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1
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Chentoufi AA, Ulmer JB, BenMohamed L. Antigen Delivery Platforms for Next-Generation Coronavirus Vaccines. Vaccines (Basel) 2024; 13:30. [PMID: 39852809 PMCID: PMC11769099 DOI: 10.3390/vaccines13010030] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2024] [Revised: 12/15/2024] [Accepted: 12/21/2024] [Indexed: 01/26/2025] Open
Abstract
The COVID-19 pandemic, caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), is in its sixth year and is being maintained by the inability of current spike-alone-based COVID-19 vaccines to prevent transmission leading to the continuous emergence of variants and sub-variants of concern (VOCs). This underscores the critical need for next-generation broad-spectrum pan-Coronavirus vaccines (pan-CoV vaccine) to break this cycle and end the pandemic. The development of a pan-CoV vaccine offering protection against a wide array of VOCs requires two key elements: (1) identifying protective antigens that are highly conserved between passed, current, and future VOCs; and (2) developing a safe and efficient antigen delivery system for induction of broad-based and long-lasting B- and T-cell immunity. This review will (1) present the current state of antigen delivery platforms involving a multifaceted approach, including bioinformatics, molecular and structural biology, immunology, and advanced computational methods; (2) discuss the challenges facing the development of safe and effective antigen delivery platforms; and (3) highlight the potential of nucleoside-modified mRNA encapsulated in lipid nanoparticles (LNP) as the platform that is well suited to the needs of a next-generation pan-CoV vaccine, such as the ability to induce broad-based immunity and amenable to large-scale manufacturing to safely provide durable protective immunity against current and future Coronavirus threats.
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Affiliation(s)
- Aziz A. Chentoufi
- Laboratory of Cellular and Molecular Immunology, Gavin Herbert Eye Institute, School of Medicine, University of California Irvine, Irvine, CA 92697, USA;
| | - Jeffrey B. Ulmer
- Department of Vaccines and Immunotherapies, TechImmune, LLC, University Lab Partners, Irvine, CA 92660, USA;
| | - Lbachir BenMohamed
- Laboratory of Cellular and Molecular Immunology, Gavin Herbert Eye Institute, School of Medicine, University of California Irvine, Irvine, CA 92697, USA;
- Department of Vaccines and Immunotherapies, TechImmune, LLC, University Lab Partners, Irvine, CA 92660, USA;
- Institute for Immunology, School of Medicine, University of California Irvine, Irvine, CA 92697, USA
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Mirjalili SZ, Tamiji Z, Shirangi M, Amini M. A GC-MS Method for Determination of β-Propiolactone Residues in Inactivated Covid-19 Vaccines. J Chromatogr Sci 2024; 62:905-911. [PMID: 39286865 DOI: 10.1093/chromsci/bmae049] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2023] [Revised: 05/23/2024] [Accepted: 08/23/2024] [Indexed: 09/19/2024]
Abstract
β-propiolactone is a common inactivator agent used in vaccines. Due to β-propiolactone carcinogenicity, complete hydrolysis of it is necessary to prevent cytotoxicity in mammalian cells. As a result, more attention should be paid to it at the clinic, and it is important to measure its trace amounts. β-propiolactone analysis is challenging due to its instability. A simple and fast gas chromatography-mass spectrometry method was developed for quantitation of residual β-propiolactone in inactivated coronavirus disease 2019 (Covid-19) vaccines. Caprolactone was used as an internal standard in sample solutions; the analysis was performed after extraction of analyte from vaccine media by ethyl acetate. The validity of the method was studied with a linearity of r2 > 0.99 over the concentration range of 0.2-20 μg/mL with the limit of detection and the limit of quantification of 0.07 and 0.20 μg/mL, respectively. The target analyte β-propiolactone was not detected in the samples, demonstrating the test samples were qualified. The established method can be used for quality control of inactivated Covid-19 vaccines.
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Affiliation(s)
- Seyedeh Zohreh Mirjalili
- Department of Drug and Food Control, Faculty of Pharmacy, Tehran University of Medical Sciences, Engelab Ave, Tehran 14155-6451, Iran
| | - Zahra Tamiji
- Department of Drug and Food Control, Faculty of Pharmacy, Tehran University of Medical Sciences, Engelab Ave, Tehran 14155-6451, Iran
- Food and Drug Administration, Tehran University of Medical Sciences, Engelab Ave, Tehran 14155-6451, Iran
| | - Mehrnoosh Shirangi
- Department of Drug and Food Control, Faculty of Pharmacy, Tehran University of Medical Sciences, Engelab Ave, Tehran 14155-6451, Iran
| | - Mohsen Amini
- Department of Medicinal Chemistry, Faculty of Pharmacy, Tehran University of Medical Sciences, Engelab Ave, Tehran 14155-6451, Iran
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3
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Nimer NA, Nimer SN. Immunization against Medically Important Human Coronaviruses of Public Health Concern. THE CANADIAN JOURNAL OF INFECTIOUS DISEASES & MEDICAL MICROBIOLOGY = JOURNAL CANADIEN DES MALADIES INFECTIEUSES ET DE LA MICROBIOLOGIE MEDICALE 2024; 2024:9952803. [PMID: 38938549 PMCID: PMC11208815 DOI: 10.1155/2024/9952803] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 10/04/2023] [Revised: 01/14/2024] [Accepted: 05/20/2024] [Indexed: 06/29/2024]
Abstract
SARS-CoV-2 is a virus that affects the human immune system. It was observed to be on the rise since the beginning of 2020 and turned into a life-threatening pandemic. Scientists have tried to develop a possible preventive and therapeutic drug against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and other related coronaviruses by assessing COVID-19-recovered persons' immunity. This study aims to review immunization against SARS-CoV-2, along with exploring the interventions that have been developed for the prevention of SARS-CoV-2. This study also highlighted the role of phototherapy in treating SARS-CoV infection. The study adopted a review approach to gathering the information available and the progress that has been made in the treatment and prevention of COVID-19. Various vaccinations, including nucleotide, subunit, and vector-based vaccines, as well as attenuated and inactivated forms that have already been shown to have prophylactic efficacy against the Middle East respiratory syndrome coronavirus (MERS-CoV) and SARS-CoV, have been summarized. Neutralizing and non-neutralizing antibodies are all associated with viral infections. Because there is no specific antiviral vaccine or therapies for coronaviruses, the main treatment strategy is supportive care, which is reinforced by combining broad-spectrum antivirals, convalescent plasma, and corticosteroids. COVID-19 has been a challenge to keep reconsidering the usual approaches to regulatory evaluation as a result of getting mixed and complicated findings on the vaccines, as well as licensing procedures. However, it is observed that medicinal herbs also play an important role in treating infection of the upper respiratory tract, the principal symptom of SARS-CoV due to their natural bioactive composite. However, some Traditional Chinese Medicines contain mutagens and nephrotoxins and the toxicological properties of the majority of Chinese herbal remedies are unknown. Therefore, to treat the COVID-19 infection along with conventional treatment, it is recommended that herb-drug interaction be examined thoroughly.
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Affiliation(s)
- Nabil A. Nimer
- Faculty of Pharmacy, Philadelphia University, Amman, Jordan
| | - Seema N. Nimer
- School of Medicine, The University of Jordan, Amman, Jordan
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Esmat K, Jamil B, Kheder RK, Kombe Kombe AJ, Zeng W, Ma H, Jin T. Immunoglobulin A response to SARS-CoV-2 infection and immunity. Heliyon 2024; 10:e24031. [PMID: 38230244 PMCID: PMC10789627 DOI: 10.1016/j.heliyon.2024.e24031] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2023] [Revised: 12/18/2023] [Accepted: 01/02/2024] [Indexed: 01/18/2024] Open
Abstract
The novel coronavirus disease (COVID-19) and its infamous "Variants" of the etiological agent termed Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2) has proven to be a global health concern. The three antibodies, IgA, IgM, and IgG, perform their dedicated role as main workhorses of the host adaptive immune system in virus neutralization. Immunoglobulin-A (IgA), also known as "Mucosal Immunoglobulin", has been under keen interest throughout the viral infection cycle. Its importance lies because IgA is predominant mucosal antibody and SARS family viruses primarily infect the mucosal surfaces of human respiratory tract. Therefore, IgA can be considered a diagnostic and prognostic marker and an active infection biomarker for SARS CoV-2 infection. Along with molecular analyses, serological tests, including IgA detection tests, are gaining ground in application as an early detectable marker and as a minimally invasive detection strategy. In the current review, it was emphasized the role of IgA response in diagnosis, host defense strategies, treatment, and prevention of SARS-CoV-2 infection. The data analysis was performed through almost 100 published peer-reviewed research reports and comprehended the importance of IgA in antiviral immunity against SARS-CoV-2 and other related respiratory viruses. Taken together, it is concluded that secretory IgA- Abs can serve as a promising detection tool for respiratory viral diagnosis and treatment parallel to IgG-based therapeutics and diagnostics. Vaccine candidates that target and trigger mucosal immune response may also be employed in future dimensions of research against other respiratory viruses.
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Affiliation(s)
- Khaleqsefat Esmat
- Department of Obstetrics and Gynecology, The First Affiliated Hospital of USTC, Center for Advanced Interdisciplinary Science and Biomedicine of IHM, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, 230001, China
| | - Baban Jamil
- Department of Medical Analysis, Faculty of Applied Science, Tishk International University, KRG, Erbil, Iraq
| | - Ramiar Kaml Kheder
- Medical Laboratory Science Department, College of Science, University of Raparin, Rania, Sulaymaniyah, Iraq
| | - Arnaud John Kombe Kombe
- Laboratory of Structural Immunology, School of Basic Medical Sciences, Division of Life Sciences and Medicine, University of Science & Technology of China, Hefei, Anhui, 230027, China
| | - Weihong Zeng
- Laboratory of Structural Immunology, School of Basic Medical Sciences, Division of Life Sciences and Medicine, University of Science & Technology of China, Hefei, Anhui, 230027, China
| | - Huan Ma
- Laboratory of Structural Immunology, School of Basic Medical Sciences, Division of Life Sciences and Medicine, University of Science & Technology of China, Hefei, Anhui, 230027, China
| | - Tengchuan Jin
- Department of Obstetrics and Gynecology, The First Affiliated Hospital of USTC, Center for Advanced Interdisciplinary Science and Biomedicine of IHM, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, 230001, China
- Laboratory of Structural Immunology, School of Basic Medical Sciences, Division of Life Sciences and Medicine, University of Science & Technology of China, Hefei, Anhui, 230027, China
- Institute of Health and Medicine, Hefei Comprehensive National Science Center, Hefei, Anhui, China
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5
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Russo M, Mendes-Corrêa MC, Lins BB, Kersten V, Pernambuco Filho PCA, Martins TR, Tozetto-Mendoza TR, Vilas Boas LS, Gomes BM, Dati LMM, Duarte-Neto AN, Reigado GR, Frederico ABT, de Brito e Cunha DRDA, de Paula AV, da Silva JIG, Vasconcelos CFM, Chambergo FS, Nunes VA, Ano Bom APD, Castilho LR, Martins RAP, Hirata MH, Mirotti L. Intranasal Liposomal Formulation of Spike Protein Adjuvanted with CpG Protects and Boosts Heterologous Immunity of hACE2 Transgenic Mice to SARS-CoV-2 Infection. Vaccines (Basel) 2023; 11:1732. [PMID: 38006064 PMCID: PMC10675295 DOI: 10.3390/vaccines11111732] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2023] [Revised: 11/05/2023] [Accepted: 11/08/2023] [Indexed: 11/26/2023] Open
Abstract
Mucosal vaccination appears to be suitable to protect against SARS-CoV-2 infection. In this study, we tested an intranasal mucosal vaccine candidate for COVID-19 that consisted of a cationic liposome containing a trimeric SARS-CoV-2 spike protein and CpG-ODNs, a Toll-like receptor 9 agonist, as an adjuvant. In vitro and in vivo experiments indicated the absence of toxicity following the intranasal administration of this vaccine formulation. First, we found that subcutaneous or intranasal vaccination protected hACE-2 transgenic mice from infection with the wild-type (Wuhan) SARS-CoV-2 strain, as shown by weight loss and mortality indicators. However, when compared with subcutaneous administration, the intranasal route was more effective in the pulmonary clearance of the virus and induced higher neutralizing antibodies and anti-S IgA titers. In addition, the intranasal vaccination afforded protection against gamma, delta, and omicron virus variants of concern. Furthermore, the intranasal vaccine formulation was superior to intramuscular vaccination with a recombinant, replication-deficient chimpanzee adenovirus vector encoding the SARS-CoV-2 spike glycoprotein (Oxford/AstraZeneca) in terms of virus lung clearance and production of neutralizing antibodies in serum and bronchial alveolar lavage (BAL). Finally, the intranasal liposomal formulation boosted heterologous immunity induced by previous intramuscular vaccination with the Oxford/AstraZeneca vaccine, which was more robust than homologous immunity.
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Affiliation(s)
- Momtchilo Russo
- Department of Immunology, Institute of Biomedical Science, University of São Paulo (ICB-USP), São Paulo 05508-000, Brazil
| | - Maria Cássia Mendes-Corrêa
- Laboratório de Virologia (LIM52), Instituto de Medicina Tropical de São Paulo, Faculdade de Medicina da Universidade de São Paulo (FM-USP), São Paulo 05403-000, Brazil; (M.C.M.-C.); (T.R.M.)
| | - Bruna B. Lins
- Department of Immunology, Institute of Biomedical Science, University of São Paulo (ICB-USP), São Paulo 05508-000, Brazil
| | - Victor Kersten
- Department of Immunology, Institute of Biomedical Science, University of São Paulo (ICB-USP), São Paulo 05508-000, Brazil
| | - Paulo C. A. Pernambuco Filho
- Department of Immunology, Institute of Biomedical Science, University of São Paulo (ICB-USP), São Paulo 05508-000, Brazil
| | - Toni Ricardo Martins
- Laboratório de Virologia (LIM52), Instituto de Medicina Tropical de São Paulo, Faculdade de Medicina da Universidade de São Paulo (FM-USP), São Paulo 05403-000, Brazil; (M.C.M.-C.); (T.R.M.)
- Faculdade de Ciências Farmacêuticas, Universidade Federal do Amazonas (UFAM), Manaus 69080-900, Brazil
| | - Tânia Regina Tozetto-Mendoza
- Laboratório de Virologia (LIM52), Instituto de Medicina Tropical de São Paulo, Faculdade de Medicina da Universidade de São Paulo (FM-USP), São Paulo 05403-000, Brazil; (M.C.M.-C.); (T.R.M.)
| | - Lucy Santos Vilas Boas
- Laboratório de Virologia (LIM52), Instituto de Medicina Tropical de São Paulo, Faculdade de Medicina da Universidade de São Paulo (FM-USP), São Paulo 05403-000, Brazil; (M.C.M.-C.); (T.R.M.)
| | - Brisa Moreira Gomes
- Department of Immunology, Institute of Biomedical Science, University of São Paulo (ICB-USP), São Paulo 05508-000, Brazil
| | - Livia Mendonça Munhoz Dati
- Departamento de Analises Clinicas e Toxicologicas, Faculdade de Ciências Farmacêuticas da Universidade de Sao Paulo (FCF-USP), São Paulo 05508-000, Brazil (M.H.H.)
| | - Amaro Nunes Duarte-Neto
- Departamento de Patologia, Faculdade de Medicina da Universidade de São Paulo (FM-USP), São Paulo 05403-000, Brazil
| | - Gustavo Roncoli Reigado
- Laboratório de Biotecnologia, Escola de Artes, Ciências e Humanidades, Universidade de São Paulo (EACH-USP), São Paulo 03828-000, Brazil (F.S.C.); (V.A.N.)
| | - Ana Beatriz T. Frederico
- Immunological Technology Laboratory, Institute of Immunobiological Technology (Bio-Manguinhos), Oswaldo Cruz Foundation (Fiocruz), Rio de Janeiro 21040-900, Brazil (A.P.D.A.B.)
| | - Danielle R. de A. de Brito e Cunha
- Immunological Technology Laboratory, Institute of Immunobiological Technology (Bio-Manguinhos), Oswaldo Cruz Foundation (Fiocruz), Rio de Janeiro 21040-900, Brazil (A.P.D.A.B.)
| | - Anderson Vicente de Paula
- Laboratório de Virologia (LIM52), Instituto de Medicina Tropical de São Paulo, Faculdade de Medicina da Universidade de São Paulo (FM-USP), São Paulo 05403-000, Brazil; (M.C.M.-C.); (T.R.M.)
| | - José Igor G. da Silva
- Programa de Biologia Celular e do Desenvolvimento, Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro 21941-902, Brazil (R.A.P.M.)
| | - Carlos F. Moreira Vasconcelos
- Programa de Biologia Celular e do Desenvolvimento, Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro 21941-902, Brazil (R.A.P.M.)
| | - Felipe S. Chambergo
- Laboratório de Biotecnologia, Escola de Artes, Ciências e Humanidades, Universidade de São Paulo (EACH-USP), São Paulo 03828-000, Brazil (F.S.C.); (V.A.N.)
| | - Viviane Abreu Nunes
- Laboratório de Biotecnologia, Escola de Artes, Ciências e Humanidades, Universidade de São Paulo (EACH-USP), São Paulo 03828-000, Brazil (F.S.C.); (V.A.N.)
| | - Ana Paula Dinis Ano Bom
- Immunological Technology Laboratory, Institute of Immunobiological Technology (Bio-Manguinhos), Oswaldo Cruz Foundation (Fiocruz), Rio de Janeiro 21040-900, Brazil (A.P.D.A.B.)
| | - Leda R. Castilho
- Cell Culture Engineering Laboratory, COPPE, Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro 21941-598, Brazil;
| | - Rodrigo A. P. Martins
- Programa de Biologia Celular e do Desenvolvimento, Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro 21941-902, Brazil (R.A.P.M.)
| | - Mario Hiroyuki Hirata
- Departamento de Analises Clinicas e Toxicologicas, Faculdade de Ciências Farmacêuticas da Universidade de Sao Paulo (FCF-USP), São Paulo 05508-000, Brazil (M.H.H.)
| | - Luciana Mirotti
- Institute of Science and Technology in Biomodels (ICTB), Oswaldo Cruz Foundation (Fiocruz), Rio de Janeiro 21040-900, Brazil
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6
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Rando HM, Lordan R, Kolla L, Sell E, Lee AJ, Wellhausen N, Naik A, Kamil JP, Gitter A, Greene CS. The Coming of Age of Nucleic Acid Vaccines during COVID-19. mSystems 2023; 8:e0092822. [PMID: 36861992 PMCID: PMC10134841 DOI: 10.1128/msystems.00928-22] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/03/2023] Open
Abstract
In the 21st century, several emergent viruses have posed a global threat. Each pathogen has emphasized the value of rapid and scalable vaccine development programs. The ongoing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has made the importance of such efforts especially clear. New biotechnological advances in vaccinology allow for recent advances that provide only the nucleic acid building blocks of an antigen, eliminating many safety concerns. During the COVID-19 pandemic, these DNA and RNA vaccines have facilitated the development and deployment of vaccines at an unprecedented pace. This success was attributable at least in part to broader shifts in scientific research relative to prior epidemics: the genome of SARS-CoV-2 was available as early as January 2020, facilitating global efforts in the development of DNA and RNA vaccines within 2 weeks of the international community becoming aware of the new viral threat. Additionally, these technologies that were previously only theoretical are not only safe but also highly efficacious. Although historically a slow process, the rapid development of vaccines during the COVID-19 crisis reveals a major shift in vaccine technologies. Here, we provide historical context for the emergence of these paradigm-shifting vaccines. We describe several DNA and RNA vaccines in terms of their efficacy, safety, and approval status. We also discuss patterns in worldwide distribution. The advances made since early 2020 provide an exceptional illustration of how rapidly vaccine development technology has advanced in the last 2 decades in particular and suggest a new era in vaccines against emerging pathogens. IMPORTANCE The SARS-CoV-2 pandemic has caused untold damage globally, presenting unusual demands on but also unique opportunities for vaccine development. The development, production, and distribution of vaccines are imperative to saving lives, preventing severe illness, and reducing the economic and social burdens caused by the COVID-19 pandemic. Although vaccine technologies that provide the DNA or RNA sequence of an antigen had never previously been approved for use in humans, they have played a major role in the management of SARS-CoV-2. In this review, we discuss the history of these vaccines and how they have been applied to SARS-CoV-2. Additionally, given that the evolution of new SARS-CoV-2 variants continues to present a significant challenge in 2022, these vaccines remain an important and evolving tool in the biomedical response to the pandemic.
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Affiliation(s)
- Halie M. Rando
- Department of Systems Pharmacology and Translational Therapeutics, University of Pennsylvania, Philadelphia, Pennsylvania, USA
- Department of Biochemistry and Molecular Genetics, University of Colorado Anschutz School of Medicine, Aurora, Colorado, USA
- Center for Health AI, University of Colorado Anschutz School of Medicine, Aurora, Colorado, USA
- Department of Biomedical Informatics, University of Colorado Anschutz School of Medicine, Aurora, Colorado, USA
| | - Ronan Lordan
- Department of Systems Pharmacology and Translational Therapeutics, University of Pennsylvania, Philadelphia, Pennsylvania, USA
- Institute for Translational Medicine and Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
- Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
| | - Likhitha Kolla
- Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
| | - Elizabeth Sell
- Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
| | - Alexandra J. Lee
- Department of Systems Pharmacology and Translational Therapeutics, University of Pennsylvania, Philadelphia, Pennsylvania, USA
| | - Nils Wellhausen
- Department of Systems Pharmacology and Translational Therapeutics, University of Pennsylvania, Philadelphia, Pennsylvania, USA
| | - Amruta Naik
- Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania, USA
| | - Jeremy P. Kamil
- Department of Microbiology and Immunology, Louisiana State University Health Sciences Center Shreveport, Shreveport, Louisiana, USA
| | - COVID-19 Review Consortium
- Department of Systems Pharmacology and Translational Therapeutics, University of Pennsylvania, Philadelphia, Pennsylvania, USA
- Department of Biochemistry and Molecular Genetics, University of Colorado Anschutz School of Medicine, Aurora, Colorado, USA
- Center for Health AI, University of Colorado Anschutz School of Medicine, Aurora, Colorado, USA
- Department of Biomedical Informatics, University of Colorado Anschutz School of Medicine, Aurora, Colorado, USA
- Institute for Translational Medicine and Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
- Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
- Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
- Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania, USA
- Department of Microbiology and Immunology, Louisiana State University Health Sciences Center Shreveport, Shreveport, Louisiana, USA
- Department of Biostatistics and Medical Informatics, University of Wisconsin—Madison, Madison, Wisconsin, USA
- Morgridge Institute for Research, Madison, Wisconsin, USA
- Childhood Cancer Data Lab, Alex’s Lemonade Stand Foundation, Philadelphia, Pennsylvania, USA
| | - Anthony Gitter
- Department of Biostatistics and Medical Informatics, University of Wisconsin—Madison, Madison, Wisconsin, USA
- Morgridge Institute for Research, Madison, Wisconsin, USA
| | - Casey S. Greene
- Department of Systems Pharmacology and Translational Therapeutics, University of Pennsylvania, Philadelphia, Pennsylvania, USA
- Department of Biochemistry and Molecular Genetics, University of Colorado Anschutz School of Medicine, Aurora, Colorado, USA
- Center for Health AI, University of Colorado Anschutz School of Medicine, Aurora, Colorado, USA
- Department of Biomedical Informatics, University of Colorado Anschutz School of Medicine, Aurora, Colorado, USA
- Childhood Cancer Data Lab, Alex’s Lemonade Stand Foundation, Philadelphia, Pennsylvania, USA
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7
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Pons S, Uhel F, Frapy E, Sérémé Y, Zafrani L, Aschard H, Skurnik D. How Protective are Antibodies to SARS-CoV-2, the Main Weapon of the B-Cell Response? Stem Cell Rev Rep 2023; 19:585-600. [PMID: 36422774 PMCID: PMC9685122 DOI: 10.1007/s12015-022-10477-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/03/2022] [Indexed: 11/25/2022]
Abstract
Since the beginning of the Coronavirus disease (COVID)-19 pandemic in December 2019, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been responsible for more than 600 million infections and 6.5 million deaths worldwide. Given the persistence of SARS-CoV-2 and its ability to develop new variants, the implementation of an effective and long-term herd immunity appears to be crucial to overcome the pandemic. While a vast field of research has focused on the role of humoral immunity against SARS-CoV-2, a growing body of evidence suggest that antibodies alone only confer a partial protection against infection of reinfection which could be of high importance regarding the strategic development goals (SDG) of the United Nations (UN) and in particular UN SDG3 that aims towards the realization of good health and well being on a global scale in the context of the COVID-19 pandemic.In this review, we highlight the role of humoral immunity in the host defense against SARS-CoV-2, with a focus on highly neutralizing antibodies. We summarize the results of the main clinical trials leading to an overall disappointing efficacy of convalescent plasma therapy, variable results of monoclonal neutralizing antibodies in patients with COVID-19 but outstanding results for the mRNA based vaccines against SARS-CoV-2. Finally, we advocate that beyond antibody responses, the development of a robust cellular immunity against SARS-CoV-2 after infection or vaccination is of utmost importance for promoting immune memory and limiting disease severity, especially in case of (re)-infection by variant viruses.
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Affiliation(s)
- Stéphanie Pons
- DMU DREAM, Department of Anesthesiology and Critical Care, Sorbonne University, GRC 29, AP-HP, Pitié-Salpêtrière, Paris, France
- Université de Paris Cité, INSERM U976- Human Immunology, Pathophysiology, Immunotherapy (HIPI), Paris, France
| | - Fabrice Uhel
- INSERM, CNRS, Institut Necker Enfants Malades, Université de Paris Cité, Paris, France
- DMU ESPRIT, Médecine Intensive Réanimation, AP-HP, Hôpital Louis Mourier, 92700, Colombes, France
| | - Eric Frapy
- INSERM, CNRS, Institut Necker Enfants Malades, Université de Paris Cité, Paris, France
| | - Youssouf Sérémé
- INSERM, CNRS, Institut Necker Enfants Malades, Université de Paris Cité, Paris, France
| | - Lara Zafrani
- Université de Paris Cité, INSERM U976- Human Immunology, Pathophysiology, Immunotherapy (HIPI), Paris, France
- Medical Intensive Care Unit, Saint Louis Hospital, Assistance Publique Hôpitaux de Paris (APHP), Université de Paris, Paris, France
| | - Hugues Aschard
- Department of Computational Biology, USR 3756 CNRS, Institut Pasteur, Paris, France
| | - David Skurnik
- INSERM, CNRS, Institut Necker Enfants Malades, Université de Paris Cité, Paris, France.
- Department of Clinical Microbiology, Necker-Enfants Malades University Hospital, Assistance Publique-Hôpitaux de Paris (APHP), Université de Paris Cité, Paris, France.
- Division of Infectious Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
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8
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Chavda VP, Bezbaruah R, Valu D, Patel B, Kumar A, Prasad S, Kakoti BB, Kaushik A, Jesawadawala M. Adenoviral Vector-Based Vaccine Platform for COVID-19: Current Status. Vaccines (Basel) 2023; 11:432. [PMID: 36851309 PMCID: PMC9965371 DOI: 10.3390/vaccines11020432] [Citation(s) in RCA: 26] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2022] [Revised: 01/27/2023] [Accepted: 01/29/2023] [Indexed: 02/16/2023] Open
Abstract
The coronavirus disease (COVID-19) breakout had an unimaginable worldwide effect in the 21st century, claiming millions of lives and putting a huge burden on the global economy. The potential developments in vaccine technologies following the determination of the genetic sequence of SARS-CoV-2 and the increasing global efforts to bring potential vaccines and therapeutics into the market for emergency use have provided a small bright spot to this tragic event. Several intriguing vaccine candidates have been developed using recombinant technology, genetic engineering, and other vaccine development technologies. In the last decade, a vast amount of the vaccine development process has diversified towards the usage of viral vector-based vaccines. The immune response elicited by such vaccines is comparatively higher than other approved vaccine candidates that require a booster dose to provide sufficient immune protection. The non-replicating adenoviral vectors are promising vaccine carriers for infectious diseases due to better yield, cGMP-friendly manufacturing processes, safety, better efficacy, manageable shipping, and storage procedures. As of April 2022, the WHO has approved a total of 10 vaccines around the world for COVID-19 (33 vaccines approved by at least one country), among which three candidates are adenoviral vector-based vaccines. This review sheds light on the developmental summary of all the adenoviral vector-based vaccines that are under emergency use authorization (EUA) or in the different stages of development for COVID-19 management.
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Affiliation(s)
- Vivek P. Chavda
- Department of Pharmaceutics and Pharmaceutical Technology, L. M. College of Pharmacy, Ahmedabad 380009, Gujarat, India
| | - Rajashri Bezbaruah
- Department of Pharmaceutical Sciences, Faculty of Science and Engineering, Dibrugarh University, Dibrugarh 786004, Assam, India
| | - Disha Valu
- Drug Product Development Laboratory, Biopharma Division, Intas Pharmaceutical Ltd., Moraiya, Ahmedabad 382213, Gujarat, India
| | - Bindra Patel
- Pharmacy Section, L. M. College of Pharmacy, Ahmedabad 380009, Gujarat, India
| | - Anup Kumar
- Pharmacy Section, L. M. College of Pharmacy, Ahmedabad 380009, Gujarat, India
| | - Sanjay Prasad
- Cell and Gene Therapy Drug Product Development Laboratory, Biopharma Division, Intas Pharmaceutical Ltd., Moraiya, Ahmedabad 382213, Gujarat, India
| | - Bibhuti Bhusan Kakoti
- Department of Pharmaceutical Sciences, Faculty of Science and Engineering, Dibrugarh University, Dibrugarh 786004, Assam, India
| | - Ajeet Kaushik
- NanoBioTech Laboratory, Health Systems Engineering, Department of Environmental Engineering, Florida Polytechnic University, Lakeland, FL 33805-8531, USA
| | - Mariya Jesawadawala
- Pharmacy Section, L. M. College of Pharmacy, Ahmedabad 380009, Gujarat, India
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9
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Molina Estupiñan JL, Aradottir Pind AA, Foroutan Pajoohian P, Jonsdottir I, Bjarnarson SP. The adjuvants dmLT and mmCT enhance humoral immune responses to a pneumococcal conjugate vaccine after both parenteral or mucosal immunization of neonatal mice. Front Immunol 2023; 13:1078904. [PMID: 36741402 PMCID: PMC9896006 DOI: 10.3389/fimmu.2022.1078904] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2022] [Accepted: 12/12/2022] [Indexed: 01/21/2023] Open
Abstract
Immaturity of the neonatal immune system contributes to increased susceptibility to infectious diseases and poor vaccine responses. Therefore, better strategies for early life vaccination are needed. Adjuvants can enhance the magnitude and duration of immune responses. In this study we assessed the effects of the adjuvants dmLT and mmCT and different immunization routes, subcutaneous (s.c.) and intranasal (i.n.), on neonatal immune response to a pneumococcal conjugate vaccine Pn1-CRM197. Pn1-specific antibody (Ab) levels of neonatal mice immunized with Pn1-CRM197 alone were low. The adjuvants enhanced IgG Ab responses up to 8 weeks after immunization, more after s.c. than i.n. immunization. On the contrary, i.n. immunization with either adjuvant enhanced serum and salivary IgA levels more than s.c. immunization. In addition, both dmLT and mmCT enhanced germinal center formation and accordingly, dmLT and mmCT enhanced the induction and persistence of Pn1-specific IgG+ Ab-secreting cells (ASCs) in spleen and bone marrow (BM), irrespective of the immunization route. Furthermore, i.n. immunization enhanced Pn1-specific IgA+ ASCs in BM more than s.c. immunizatiofimmu.2022.1078904n. However, a higher i.n. dose of the Pn1-CRM197 was needed to achieve IgG response comparable to that elicited by s.c. immunization with either adjuvant. We conclude that dmLT and mmCT enhance both induction and persistence of the neonatal immune response to the vaccine Pn1-CRM197, following mucosal or parenteral immunization. This indicates that dmLT and mmCT are promising adjuvants for developing safe and effective early life vaccination strategies.
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Affiliation(s)
- Jenny Lorena Molina Estupiñan
- Department of Immunology, Landspitali, The National University Hospital of Iceland, Reykjavik, Iceland,Faculty of Medicine, School of Health Sciences, University of Iceland, Reykjavik, Iceland
| | - Audur Anna Aradottir Pind
- Department of Immunology, Landspitali, The National University Hospital of Iceland, Reykjavik, Iceland,Faculty of Medicine, School of Health Sciences, University of Iceland, Reykjavik, Iceland
| | - Poorya Foroutan Pajoohian
- Department of Immunology, Landspitali, The National University Hospital of Iceland, Reykjavik, Iceland,Faculty of Medicine, School of Health Sciences, University of Iceland, Reykjavik, Iceland
| | - Ingileif Jonsdottir
- Department of Immunology, Landspitali, The National University Hospital of Iceland, Reykjavik, Iceland,Faculty of Medicine, School of Health Sciences, University of Iceland, Reykjavik, Iceland
| | - Stefania P. Bjarnarson
- Department of Immunology, Landspitali, The National University Hospital of Iceland, Reykjavik, Iceland,Faculty of Medicine, School of Health Sciences, University of Iceland, Reykjavik, Iceland,*Correspondence: Stefania P. Bjarnarson,
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10
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Lai D, Xue J, He P, Jiang H, Li Y, Ma M, Hong W, Yu J, Wei H, Tao S. Longitudinal neutralization activities on authentic Omicron variant provided by three doses of BBIBP-CorV vaccination during one year. Proteomics 2023; 23:e2200306. [PMID: 36205637 PMCID: PMC9874883 DOI: 10.1002/pmic.202200306] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2022] [Revised: 09/18/2022] [Accepted: 09/28/2022] [Indexed: 01/27/2023]
Abstract
The majority of people in China have been immunized with the inactivated viral vaccine BBIBP-CorV. The emergence of the Omicron variant raised the concerns about protection efficacy of the inactivated viral vaccine in China. However, longitudinal neutralization data describing protection efficacy against Omicron variant is still lacking. Here we present one-year longitudinal neutralization data of BBIBP-CorV on authentic Omicron, Delta, and wild-type strains using 224 sera collected from 14 volunteers who have finished three doses BBIBP-CorV. The sera were also subjected for monitoring the SARS-CoV-2 specific IgG, IgA, and IgM responses on protein and peptide microarrays. The neutralization titers showed different protection efficacies against the three strains. By incorporating IgG and IgA signals of proteins and Spike protein derived peptide on microarray, panels as potential surrogate biomarkers for rapid estimation of neutralization titers were established. These data support the necessity of the 3rd dose of BBIBP-CorV vaccination. After further validation and assay development, the panels could be used for reliable, convenient and fast evaluation of the efficacy of vaccination.
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Affiliation(s)
- Dan‐yun Lai
- Key Laboratory of Systems Biomedicine (Ministry of Education), Shanghai Center for Systems BiomedicineShanghai Jiao Tong UniversityShanghaiChina
| | - Jun‐biao Xue
- Key Laboratory of Systems Biomedicine (Ministry of Education), Shanghai Center for Systems BiomedicineShanghai Jiao Tong UniversityShanghaiChina
| | - Ping He
- CAS Key Laboratory of Special Pathogens and Biosafety, Centre for Biosafety Mega‐Science, Wuhan Institute of VirologyChinese Academy of SciencesWuhanHubeiChina,University of Chinese Academy of SciencesBeijingChina
| | - He‐wei Jiang
- Key Laboratory of Systems Biomedicine (Ministry of Education), Shanghai Center for Systems BiomedicineShanghai Jiao Tong UniversityShanghaiChina
| | - Yang Li
- Key Laboratory of Systems Biomedicine (Ministry of Education), Shanghai Center for Systems BiomedicineShanghai Jiao Tong UniversityShanghaiChina
| | - Ming‐liang Ma
- Key Laboratory of Systems Biomedicine (Ministry of Education), Shanghai Center for Systems BiomedicineShanghai Jiao Tong UniversityShanghaiChina
| | - Wei Hong
- CAS Key Laboratory of Special Pathogens and Biosafety, Centre for Biosafety Mega‐Science, Wuhan Institute of VirologyChinese Academy of SciencesWuhanHubeiChina,University of Chinese Academy of SciencesBeijingChina
| | - Jun‐ping Yu
- CAS Key Laboratory of Special Pathogens and Biosafety, Centre for Biosafety Mega‐Science, Wuhan Institute of VirologyChinese Academy of SciencesWuhanHubeiChina
| | - Hong‐ping Wei
- CAS Key Laboratory of Special Pathogens and Biosafety, Centre for Biosafety Mega‐Science, Wuhan Institute of VirologyChinese Academy of SciencesWuhanHubeiChina
| | - Sheng‐ce Tao
- Key Laboratory of Systems Biomedicine (Ministry of Education), Shanghai Center for Systems BiomedicineShanghai Jiao Tong UniversityShanghaiChina
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11
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Jansen EM, Frijlink HW, Hinrichs WLJ, Ruigrok MJR. Are inhaled mRNA vaccines safe and effective? A review of preclinical studies. Expert Opin Drug Deliv 2022; 19:1471-1485. [DOI: 10.1080/17425247.2022.2131767] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022]
Affiliation(s)
- Evalyne M Jansen
- Department of Pharmaceutical Technology and Biopharmacy, University of Groningen, Groningen, The Netherlands
| | - Henderik W Frijlink
- Department of Pharmaceutical Technology and Biopharmacy, University of Groningen, Groningen, The Netherlands
| | - Wouter LJ Hinrichs
- Department of Pharmaceutical Technology and Biopharmacy, University of Groningen, Groningen, The Netherlands
| | - Mitchel JR Ruigrok
- Department of Pharmaceutical Technology and Biopharmacy, University of Groningen, Groningen, The Netherlands
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12
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Lam JH, Shivhare D, Chia TW, Chew SL, Sinsinbar G, Aw TY, Wong S, Venkataraman S, Lim FWI, Vandepapeliere P, Nallani M. Artificial Cell Membrane Polymersome-Based Intranasal Beta Spike Formulation as a Second Generation Covid-19 Vaccine. ACS NANO 2022; 16:16757-16775. [PMID: 36223228 PMCID: PMC9578649 DOI: 10.1021/acsnano.2c06350] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/27/2022] [Accepted: 10/06/2022] [Indexed: 05/25/2023]
Abstract
Current parenteral coronavirus disease 2019 (Covid-19) vaccines inadequately protect against infection of the upper respiratory tract. Additionally, antibodies generated by wild type (WT) spike-based vaccines poorly neutralize severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants. To address the need for a second-generation vaccine, we have initiated a preclinical program to produce and evaluate a potential candidate. Our vaccine consists of recombinant Beta spike protein coadministered with synthetic CpG adjuvant. Both components are encapsulated within artificial cell membrane (ACM) polymersomes, synthetic nanovesicles efficiently internalized by antigen presenting cells, including dendritic cells, enabling targeted delivery of cargo for enhanced immune responses. ACM vaccine is immunogenic in C57BL/6 mice and Golden Syrian hamsters, evoking high serum IgG and neutralizing responses. Compared to an ACM-WT spike vaccine that generates predominantly WT-neutralizing antibodies, the ACM-Beta spike vaccine induces antibodies that neutralize WT and Beta viruses equally. Intramuscular (IM)-immunized hamsters are strongly protected from weight loss and other clinical symptoms after the Beta challenge but show delayed viral clearance in the upper airway. With intranasal (IN) immunization, however, neutralizing antibodies are generated in the upper airway concomitant with rapid and potent reduction of viral load. Moreover, antibodies are cross-neutralizing and show good activity against Omicron. Safety is evaluated in New Zealand white rabbits in a repeated dose toxicological study under Good Laboratory Practice (GLP) conditions. Three doses, IM or IN, at two-week intervals do not induce an adverse effect or systemic toxicity. Cumulatively, these results support the application for a Phase 1 clinical trial of ACM-polymersome-based Covid-19 vaccine (ClinicalTrials.gov identifier: NCT05385991).
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Affiliation(s)
- Jian Hang Lam
- ACM Biolabs Pte Ltd., 71
Nanyang Drive, #02M-02, NTU Innovation Center, 638075, Singapore
| | - Devendra Shivhare
- ACM Biolabs Pte Ltd., 71
Nanyang Drive, #02M-02, NTU Innovation Center, 638075, Singapore
| | - Teck Wan Chia
- ACM Biolabs Pte Ltd., 71
Nanyang Drive, #02M-02, NTU Innovation Center, 638075, Singapore
| | - Suet Li Chew
- ACM Biolabs Pte Ltd., 71
Nanyang Drive, #02M-02, NTU Innovation Center, 638075, Singapore
| | - Gaurav Sinsinbar
- ACM Biolabs Pte Ltd., 71
Nanyang Drive, #02M-02, NTU Innovation Center, 638075, Singapore
| | - Ting Yan Aw
- ACM Biolabs Pte Ltd., 71
Nanyang Drive, #02M-02, NTU Innovation Center, 638075, Singapore
| | - Siamy Wong
- ACM Biolabs Pte Ltd., 71
Nanyang Drive, #02M-02, NTU Innovation Center, 638075, Singapore
| | - Shrinivas Venkataraman
- ACM Biolabs Pte Ltd., 71
Nanyang Drive, #02M-02, NTU Innovation Center, 638075, Singapore
| | - Francesca Wei Inng Lim
- Department of Hematology, Singapore General
Hospital, Outram Road, Block 7, Level 2, 169608,
Singapore
| | | | - Madhavan Nallani
- ACM Biolabs Pte Ltd., 71
Nanyang Drive, #02M-02, NTU Innovation Center, 638075, Singapore
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13
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Harnessing Nasal Immunity with IgA to Prevent Respiratory Infections. IMMUNO 2022. [DOI: 10.3390/immuno2040036] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/07/2022] Open
Abstract
The nasal cavity is a primary checkpoint for the invasion of respiratory pathogens. Numerous pathogens, including SARS-CoV-2, S. pneumoniae, S. aureus, etc., can adhere/colonize nasal lining to trigger an infection. Secretory IgA (sIgA) serves as the first line of immune defense against foreign pathogens. sIgA facilitates clearance of pathogenic microbes by intercepting their access to epithelial receptors and mucus entrapment through immune exclusion. Elevated levels of neutralizing IgA at the mucosal surfaces are associated with a high level of protection following intranasal immunizations. This review summarizes recent advances in intranasal vaccination technology and challenges in maintaining nominal IgA levels at the mucosal surface. Overall, the review emphasizes the significance of IgA-mediated nasal immunity, which holds a tremendous potential to mount protection against respiratory pathogens.
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14
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Araújo NM, Rubio IGS, Toneto NPA, Morale MG, Tamura RE. The use of adenoviral vectors in gene therapy and vaccine approaches. Genet Mol Biol 2022; 45:e20220079. [PMID: 36206378 PMCID: PMC9543183 DOI: 10.1590/1678-4685-gmb-2022-0079] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2022] [Accepted: 07/12/2022] [Indexed: 11/04/2022] Open
Abstract
Adenovirus was first identified in the 1950s and since then this pathogenic group
of viruses has been explored and transformed into a genetic transfer vehicle.
Modification or deletion of few genes are necessary to transform it into a
conditionally or non-replicative vector, creating a versatile tool capable of
transducing different tissues and inducing high levels of transgene expression.
In the early years of vector development, the application in monogenic diseases
faced several hurdles, including short-term gene expression and even a fatality.
On the other hand, an adenoviral delivery strategy for treatment of cancer was
the first approved gene therapy product. There is an increasing interest in
expressing transgenes with therapeutic potential targeting the cancer hallmarks,
inhibiting metastasis, inducing cancer cell death or modulating the immune
system to attack the tumor cells. Replicative adenovirus as vaccines may be even
older and date to a few years of its discovery, application of non-replicative
adenovirus for vaccination against different microorganisms has been
investigated, but only recently, it demonstrated its full potential being one of
the leading vaccination tools for COVID-19. This is not a new vector nor a new
technology, but the result of decades of careful and intense work in this
field.
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Affiliation(s)
- Natália Meneses Araújo
- Universidade Federal de São Paulo, Laboratório de Biologia Molecular
do Câncer, São Paulo, SP, Brazil.
| | - Ileana Gabriela Sanchez Rubio
- Universidade Federal de São Paulo, Laboratório de Biologia Molecular
do Câncer, São Paulo, SP, Brazil. ,Universidade Federal de São Paulo, Departamento de Ciências
Biológicas, Diadema, SP, Brazil. ,Universidade Federal de São Paulo, Laboratório de Ciências
Moleculares da Tireóide, Diadema, SP, Brazil.
| | | | - Mirian Galliote Morale
- Universidade Federal de São Paulo, Laboratório de Biologia Molecular
do Câncer, São Paulo, SP, Brazil. ,Universidade Federal de São Paulo, Departamento de Ciências
Biológicas, Diadema, SP, Brazil. ,Universidade Federal de São Paulo, Laboratório de Ciências
Moleculares da Tireóide, Diadema, SP, Brazil.
| | - Rodrigo Esaki Tamura
- Universidade Federal de São Paulo, Laboratório de Biologia Molecular
do Câncer, São Paulo, SP, Brazil. ,Universidade Federal de São Paulo, Departamento de Ciências
Biológicas, Diadema, SP, Brazil.
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15
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Waning of SARS-CoV-2 Seropositivity among Healthy Young Adults over Seven Months. Vaccines (Basel) 2022; 10:vaccines10091532. [PMID: 36146610 PMCID: PMC9505545 DOI: 10.3390/vaccines10091532] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2022] [Revised: 09/03/2022] [Accepted: 09/09/2022] [Indexed: 01/19/2023] Open
Abstract
Background: We conducted a longitudinal study to estimate immunity produced in response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection among university students over seven months. Methods: All participants were attending a public university and resided in Pitt County, North Carolina. University students enrolled weekly for 10 weeks between 26 August 2020 and 28 October 2020, resulting in 136 young adults completing at least one study visit by 17 November 2020. Enrolled students completed an online survey and nasal swab collection at two-week intervals and monthly blood collection between 26 August 2020 and 31 March 2021. Results: Amongst 695 serum samples tested during follow-up, the prevalence of a positive result for anti-nucleocapsid antibodies (N-IgG) was 9.78%. In 22 students with more than one positive N-IgG serum sample, 68.1% of the group lost persistence of N-IgG below the positive threshold over 140 days. Anti-spike IgG antibodies were significantly higher among 11 vaccinated compared to 10 unvaccinated. Conclusions: In healthy young adults, N-IgG wanes below the detectable threshold within five months. S-IgG titer remained consistently elevated months after infection, and significantly increased after vaccination.
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16
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Pérez P, Astorgano D, Albericio G, Flores S, Sánchez-Cordón PJ, Luczkowiak J, Delgado R, Casasnovas JM, Esteban M, García-Arriaza J. Intranasal administration of a single dose of MVA-based vaccine candidates against COVID-19 induced local and systemic immune responses and protects mice from a lethal SARS-CoV-2 infection. Front Immunol 2022; 13:995235. [PMID: 36172368 PMCID: PMC9510595 DOI: 10.3389/fimmu.2022.995235] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2022] [Accepted: 08/19/2022] [Indexed: 11/13/2022] Open
Abstract
Current coronavirus disease-19 (COVID-19) vaccines are administered by the intramuscular route, but this vaccine administration failed to prevent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus infection in the upper respiratory tract, mainly due to the absence of virus-specific mucosal immune responses. It is hypothesized that intranasal (IN) vaccination could induce both mucosal and systemic immune responses that blocked SARS-CoV-2 transmission and COVID-19 progression. Here, we evaluated in mice IN administration of three modified vaccinia virus Ankara (MVA)-based vaccine candidates expressing the SARS-CoV-2 spike (S) protein, either the full-length native S or a prefusion-stabilized [S(3P)] protein; SARS-CoV-2-specific immune responses and efficacy were determined after a single IN vaccine application. Results showed that in C57BL/6 mice, MVA-based vaccine candidates elicited S-specific IgG and IgA antibodies in serum and bronchoalveolar lavages, respectively, and neutralizing antibodies against parental and SARS-CoV-2 variants of concern (VoC), with MVA-S(3P) being the most immunogenic vaccine candidate. IN vaccine administration also induced polyfunctional S-specific Th1-skewed CD4+ and cytotoxic CD8+ T-cell immune responses locally (in lungs and bronchoalveolar lymph nodes) or systemically (in spleen). Remarkably, a single IN vaccine dose protected susceptible K18-hACE2 transgenic mice from morbidity and mortality caused by SARS-CoV-2 infection, with MVA-S(3P) being the most effective candidate. Infectious SARS-CoV-2 viruses were undetectable in lungs and nasal washes, correlating with high titers of S-specific IgGs and neutralizing antibodies against parental SARS-CoV-2 and several VoC. Moreover, low histopathological lung lesions and low levels of pro-inflammatory cytokines in lungs and nasal washes were detected in vaccinated animals. These results demonstrated that a single IN inoculation of our MVA-based vaccine candidates induced potent immune responses, either locally or systemically, and protected animal models from COVID-19. These results also identified an effective vaccine administration route to induce mucosal immunity that should prevent SARS-CoV-2 host-to-host transmission.
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Affiliation(s)
- Patricia Pérez
- Department of Molecular and Cellular Biology, Centro Nacional de Biotecnología (CNB), Consejo Superior de Investigaciones Científicas (CSIC), Madrid, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (CIBERINFEC), Madrid, Spain
| | - David Astorgano
- Department of Molecular and Cellular Biology, Centro Nacional de Biotecnología (CNB), Consejo Superior de Investigaciones Científicas (CSIC), Madrid, Spain
| | - Guillermo Albericio
- Department of Molecular and Cellular Biology, Centro Nacional de Biotecnología (CNB), Consejo Superior de Investigaciones Científicas (CSIC), Madrid, Spain
| | - Sara Flores
- Department of Molecular and Cellular Biology, Centro Nacional de Biotecnología (CNB), Consejo Superior de Investigaciones Científicas (CSIC), Madrid, Spain
| | - Pedro J. Sánchez-Cordón
- Pathology Department, Centro de Investigación en Sanidad Animal (CISA), Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria (INIA), Consejo Superior de Investigaciones Científicas (CSIC), Madrid, Spain
| | - Joanna Luczkowiak
- Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (CIBERINFEC), Madrid, Spain
- Department of Microbiology, Instituto de Investigación Hospital Universitario 12 de Octubre (imas12), Madrid, Spain
| | - Rafael Delgado
- Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (CIBERINFEC), Madrid, Spain
- Department of Microbiology, Instituto de Investigación Hospital Universitario 12 de Octubre (imas12), Madrid, Spain
- Department of Medicine, School of Medicine, Universidad Complutense de Madrid, Madrid, Spain
| | - José M. Casasnovas
- Department of Macromolecular Structures, Centro Nacional de Biotecnología (CNB), Consejo Superior de Investigaciones Científicas (CSIC), Madrid, Spain
| | - Mariano Esteban
- Department of Molecular and Cellular Biology, Centro Nacional de Biotecnología (CNB), Consejo Superior de Investigaciones Científicas (CSIC), Madrid, Spain
- *Correspondence: Mariano Esteban, ; Juan García-Arriaza,
| | - Juan García-Arriaza
- Department of Molecular and Cellular Biology, Centro Nacional de Biotecnología (CNB), Consejo Superior de Investigaciones Científicas (CSIC), Madrid, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (CIBERINFEC), Madrid, Spain
- *Correspondence: Mariano Esteban, ; Juan García-Arriaza,
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17
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Kumar A, Ladha A, Choudhury A, Ikbal AMA, Bhattacharjee B, Das T, Gupta G, Sharma C, Sarbajna A, Mandal SC, Choudhury MD, Ali N, Slama P, Rezaei N, Palit P, Tiwari ON. The chimera of S1 and N proteins of SARS-CoV-2: can it be a potential vaccine candidate for COVID-19? Expert Rev Vaccines 2022; 21:1071-1086. [PMID: 35604776 DOI: 10.1080/14760584.2022.2081156] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022]
Abstract
INTRODUCTION Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has emerged as one of the biggest global health issues. Spike protein (S) and nucleoprotein (N), the major immunogenic components of SARS-CoV-2, have been shown to be involved in the attachment and replication of the virus inside the host cell. AREAS COVERED Several investigations have shown that the SARS-CoV-2 nucleoprotein can elicit a cell-mediated immune response capable of regulating viral replication and lowering viral burden. However, the development of an effective vaccine that can stop the transmission of SARS-CoV-2 remains a matter of concern. Literature was retrieved using the keywords COVID-19 vaccine, role of nucleoprotein as vaccine candidate, spike protein, nucleoprotein immune responses against SARS-CoV-2, and chimera vaccine in PubMed, Google Scholar, and Google. EXPERT OPINION We have focussed on the use of chimera protein, consisting of N and S-1 protein components of SARS-CoV-2, as a potential vaccine candidate. This may act as a polyvalent mixed recombinant protein vaccine to elicit a strong T and B cell immune response, which will be capable of neutralizing the wild and mutated variants of SARS-CoV-2, and also restricting its attachment, replication, and budding in the host cell.
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Affiliation(s)
- Amresh Kumar
- Department of Life Sciences and Bioinformatics, Assam University, Silchar, India
| | - Amit Ladha
- Area of Biotechnology and Bioinformatics, NIIT University, Neemrana, India
| | - Ankita Choudhury
- Department of Pharmaceutical Sciences, Allama TR College of Pharmacy, Hospital Rd, Srigouri, India
| | - Abu Md Ashif Ikbal
- Department of Pharmacy, Tripura University (A Central University), Suryamaninagar, Tripura (W), India
| | - Bedanta Bhattacharjee
- Department of Pharmaceutical Sciences, Faculty of Science and Engineering, Dibrugarh University, Dibrugarh, India
| | - Tanmay Das
- Department of Business Administration, Assam University Silchar, India
| | - Gaurav Gupta
- Area of Biotechnology and Bioinformatics, NIIT University, Neemrana, India.,Department of Immunology, University of Manitoba, Winnipeg, Manitoba, Canada
| | - Chhavi Sharma
- Area of Biotechnology and Bioinformatics, NIIT University, Neemrana, India
| | - Adity Sarbajna
- Department of Zoology, Surendranath College, Kolkata, India
| | - Subhash C Mandal
- Department of Pharmaceutical Technology, Jadavpur University, Kolkata, India
| | | | - Nahid Ali
- Division of Immunology, Department of Infectious Diseases, INDIAN INSTITUTE OF CHEMICAL BIOLOGY, Kolkata, India
| | - Petr Slama
- Laboratory of Animal Immunology and Biotechnology, Department of Animal Morphology, Physiology and Genetics, Faculty of AgriSciences, Mendel University in Brno, Zemedelska 1, Brno, Czech Republic
| | - Nima Rezaei
- Research Center for Immunodeficiencies, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran.,Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.,Network of Immunity in Infection, Malignancy and Autoimmunity (NIIMA), Universal Scientific Education and Research Network (USERN), Stockholm, Sweden
| | - Partha Palit
- Department of Pharmaceutical Sciences Drug Discovery research Laboratory, Assam University, Silchar, India
| | - Onkar Nath Tiwari
- Centre for Conservation and Utilisation of Blue Green Algae (CCUBGA), Division of Microbiology, ICAR-Indian Agricultural Research Institute (IARI), New Delhi, India
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18
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Tioni MF, Jordan R, Pena AS, Garg A, Wu D, Phan SI, Weiss CM, Cheng X, Greenhouse J, Orekov T, Valentin D, Kar S, Pessaint L, Andersen H, Stobart CC, Bloodworth MH, Stokes Peebles R, Liu Y, Xie X, Shi PY, Moore ML, Tang RS. Mucosal administration of a live attenuated recombinant COVID-19 vaccine protects nonhuman primates from SARS-CoV-2. NPJ Vaccines 2022; 7:85. [PMID: 35906244 PMCID: PMC9334537 DOI: 10.1038/s41541-022-00509-6] [Citation(s) in RCA: 25] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2021] [Accepted: 07/01/2022] [Indexed: 12/23/2022] Open
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the COVID-19 global pandemic. SARS-CoV-2 is an enveloped RNA virus that relies on its trimeric surface glycoprotein spike for entry into host cells. Here we describe the COVID-19 vaccine candidate MV-014-212, a live, attenuated, recombinant human respiratory syncytial virus expressing a chimeric SARS-CoV-2 spike as the only viral envelope protein. MV-014-212 was attenuated and immunogenic in African green monkeys (AGMs). One mucosal administration of MV-014-212 in AGMs protected against SARS-CoV-2 challenge, reducing by more than 200-fold the peak shedding of SARS-CoV-2 in the nose. MV-014-212 elicited mucosal immunoglobulin A in the nose and neutralizing antibodies in serum that exhibited cross-neutralization against virus variants of concern Alpha, Beta, and Delta. Intranasally delivered, live attenuated vaccines such as MV-014-212 entail low-cost manufacturing suitable for global deployment. MV-014-212 is currently in Phase 1 clinical trials as an intranasal COVID-19 vaccine.
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Affiliation(s)
| | - Robert Jordan
- Meissa Vaccines Inc, Redwood City, CA, USA.,Bill & Melinda Gates Foundation, Seattle, WA, USA
| | | | | | - Danlu Wu
- Meissa Vaccines Inc, Redwood City, CA, USA
| | | | | | - Xing Cheng
- Meissa Vaccines Inc, Redwood City, CA, USA
| | | | | | | | | | | | | | | | - Melissa H Bloodworth
- Division of Allergy, Pulmonary and Critical Care Medicine, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN, USA
| | - R Stokes Peebles
- Division of Allergy, Pulmonary and Critical Care Medicine, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN, USA.,Department of Pathology, Microbiology, and Immunology, Vanderbilt University School of Medicine, Nashville, TN, USA
| | - Yang Liu
- Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, TX, USA
| | - Xuping Xie
- Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, TX, USA
| | - Pei-Yong Shi
- Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, TX, USA
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19
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Sabino JS, Amorim MR, de Souza WM, Marega LF, Mofatto LS, Toledo-Teixeira DA, Forato J, Stabeli RG, Costa ML, Spilki FR, Sabino EC, Faria NR, Benites BD, Addas-Carvalho M, Stucchi RSB, Vasconcelos DM, Weaver SC, Granja F, Proenca-Modena JL, Vilela MMDS. Clearance of Persistent SARS-CoV-2 RNA Detection in a NFκB-Deficient Patient in Association with the Ingestion of Human Breast Milk: A Case Report. Viruses 2022; 14:1042. [PMID: 35632784 PMCID: PMC9143223 DOI: 10.3390/v14051042] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2022] [Revised: 05/05/2022] [Accepted: 05/06/2022] [Indexed: 02/01/2023] Open
Abstract
Currently, there are no evidence-based treatment options for long COVID-19, and it is known that SARS-CoV-2 can persist in part of the infected patients, especially those with immunosuppression. Since there is a robust secretion of SARS-CoV-2-specific highly-neutralizing IgA antibodies in breast milk, and because this immunoglobulin plays an essential role against respiratory virus infection in mucosa cells, being, in addition, more potent in neutralizing SARS-CoV-2 than IgG, here we report the clinical course of an NFκB-deficient patient chronically infected with the SARS-CoV-2 Gamma variant, who, after a non-full effective treatment with plasma infusion, received breast milk from a vaccinated mother by oral route as treatment for COVID-19. After such treatment, the symptoms improved, and the patient was systematically tested negative for SARS-CoV-2. Thus, we hypothesize that IgA and IgG secreted antibodies present in breast milk could be useful to treat persistent SARS-CoV-2 infection in immunodeficient patients.
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Affiliation(s)
- Janine S. Sabino
- Laboratory of Pediatric Immunology, Center for Investigation in Pediatrics, Faculty of Medical Sciences, University of Campinas, Campinas 13083-887, Brazil; (J.S.S.); (L.F.M.)
| | - Mariene R. Amorim
- Laboratory of Emerging Viruses, Department of Genetics, Microbiology and Immunology, Institute of Biology, University of Campinas, Campinas 13083-862, Brazil; (M.R.A.); (L.S.M.); (D.A.T.-T.); (J.F.); (F.G.)
| | - William M. de Souza
- World Reference Center for Emerging Viruses, Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555, USA; (W.M.d.S.); (S.C.W.)
| | - Lia F. Marega
- Laboratory of Pediatric Immunology, Center for Investigation in Pediatrics, Faculty of Medical Sciences, University of Campinas, Campinas 13083-887, Brazil; (J.S.S.); (L.F.M.)
| | - Luciana S. Mofatto
- Laboratory of Emerging Viruses, Department of Genetics, Microbiology and Immunology, Institute of Biology, University of Campinas, Campinas 13083-862, Brazil; (M.R.A.); (L.S.M.); (D.A.T.-T.); (J.F.); (F.G.)
| | - Daniel A. Toledo-Teixeira
- Laboratory of Emerging Viruses, Department of Genetics, Microbiology and Immunology, Institute of Biology, University of Campinas, Campinas 13083-862, Brazil; (M.R.A.); (L.S.M.); (D.A.T.-T.); (J.F.); (F.G.)
| | - Julia Forato
- Laboratory of Emerging Viruses, Department of Genetics, Microbiology and Immunology, Institute of Biology, University of Campinas, Campinas 13083-862, Brazil; (M.R.A.); (L.S.M.); (D.A.T.-T.); (J.F.); (F.G.)
| | - Rodrigo G. Stabeli
- Oswaldo Cruz Foundation (Fiocruz-SP), Ribeirão Preto 14049-900, Brazil;
- Department of Public Health Emergency, Preparedness and Disaster, PAHO/WHO, Brasilia 70312-970, Brazil
| | - Maria Laura Costa
- Department of Obstetrics and Gynecology, Faculty of Medical Sciences, University of Campinas, Campinas 13083-887, Brazil;
| | - Fernando R. Spilki
- One Health Laboratory, Feevale University, Novo Hamburgo 93510-235, Brazil;
| | - Ester C. Sabino
- Tropical Medicine Institute, Medical School, University of São Paulo, São Paulo 5403-907, Brazil;
- Department of Infectious and Parasitic Disease, Medical School, University of São Paulo, São Paulo 05403-000, Brazil;
| | - Nuno R. Faria
- Department of Infectious and Parasitic Disease, Medical School, University of São Paulo, São Paulo 05403-000, Brazil;
- Department of Zoology, University of Oxford, Oxford OX1 2JD, UK
- MRC Centre for Global Infectious Disease Analysis, J-IDEA, Imperial College London, London SW7 2AZ, UK
| | - Bruno D. Benites
- Hematology and Transfusion Medicine Center, University of Campinas, Campinas 13083-878, Brazil; (B.D.B.); (M.A.-C.)
| | - Marcelo Addas-Carvalho
- Hematology and Transfusion Medicine Center, University of Campinas, Campinas 13083-878, Brazil; (B.D.B.); (M.A.-C.)
| | - Raquel S. B. Stucchi
- Division of Infectious Diseases, University of Campinas, Campinas 13083-887, Brazil;
| | - Dewton M. Vasconcelos
- Laboratory of Investigation in Dermatology and Immunodeficiencies, Department of Dermatology, Medical School, University of São Paulo, São Paulo 05403-000, Brazil;
| | - Scott C. Weaver
- World Reference Center for Emerging Viruses, Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555, USA; (W.M.d.S.); (S.C.W.)
- Institute for Human Infection and Immunity, University of Texas Medical Branch, Galveston, TX 77555, USA
| | - Fabiana Granja
- Laboratory of Emerging Viruses, Department of Genetics, Microbiology and Immunology, Institute of Biology, University of Campinas, Campinas 13083-862, Brazil; (M.R.A.); (L.S.M.); (D.A.T.-T.); (J.F.); (F.G.)
- Biodiversity Research Centre, Federal University of Roraima, Boa Vista 72000-000, Brazil
| | - José Luiz Proenca-Modena
- Laboratory of Emerging Viruses, Department of Genetics, Microbiology and Immunology, Institute of Biology, University of Campinas, Campinas 13083-862, Brazil; (M.R.A.); (L.S.M.); (D.A.T.-T.); (J.F.); (F.G.)
- Experimental Medicine Research Cluster (EMRC), University of Campinas, Campinas 13083-862, Brazil
- Hub of Global Health (HGH), University of Campinas, Campinas 13083-862, Brazil
| | - Maria Marluce dos S. Vilela
- Laboratory of Pediatric Immunology, Center for Investigation in Pediatrics, Faculty of Medical Sciences, University of Campinas, Campinas 13083-887, Brazil; (J.S.S.); (L.F.M.)
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20
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Gasmi A, Srinath S, Dadar M, Pivina L, Menzel A, Benahmed AG, Chirumbolo S, Bjørklund G. A global survey in the developmental landscape of possible vaccination strategies for COVID-19. Clin Immunol 2022; 237:108958. [PMID: 35218966 PMCID: PMC8865932 DOI: 10.1016/j.clim.2022.108958] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2021] [Revised: 02/13/2022] [Accepted: 02/19/2022] [Indexed: 01/04/2023]
Abstract
The development of COVID-19 vaccines was promptly regulated to ensure the best possible approach. By January 2022, 75 candidates reached preclinical evaluation in various animal models, 114 vaccines were in clinical trials on humans, and 48 were in the final testing stages. Vaccine platforms range from whole virus vaccines to nucleic acid vaccines, which are the most promising in prompt availability and safety. The USA and Europe have approved vaccines developed by Pfizer-BioNTech (BNT162b2) and Moderna (mRNa1273). So far, Pfizer-BioNTech, Moderna, Johnson & Johnson, AstraZeneca-University of Oxford, Sinopharm, Sinovac Biotech Gamaleya, Bharat Biotech, and Novavax have documented effective vaccines. Even with technological advances and a fast-paced development approach, many limitations and problems need to be overcome before a large-scale production of new vaccines can start. The Key is to ensure equal and fair distribution globally through regulatory measures. Recent studies link Bacillus Calmette-Guérin (BCG) vaccination programs and lower disease severity.
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Affiliation(s)
- Amin Gasmi
- Société Francophone de Nutrithérapie et de Nutrigénétique Appliquée, Villeurbanne, France
| | - Shvetha Srinath
- Société Francophone de Nutrithérapie et de Nutrigénétique Appliquée, Villeurbanne, France
| | - Maryam Dadar
- Razi Vaccine and Serum Research Institute, Agricultural Research, Education and Extension Organization (AREEO), Karaj, Iran
| | - Lyudmila Pivina
- Semey Medical University, Semey, Kazakhstan; CONEM Kazakhstan Environmental Health and Safety Research Group, Semey Medical University, Semey, Kazakhstan
| | | | - Asma Gasmi Benahmed
- Université Claude Bernard, Villeurbanne, France; Académie Internationale de Médecine Dentaire Intégrative, Paris, France
| | - Salvatore Chirumbolo
- Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, Verona, Italy; CONEM Scientific Secretary, Verona, Italy
| | - Geir Bjørklund
- Council for Nutritional and Environmental Medicine (CONEM), Mo i Rana, Norway.
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21
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Ren C, Gao Y, Zhang C, Zhou C, Hong Y, Qu M, Zhao Z, Du Y, Yang L, Liu B, Wang S, Han M, Shen Y, Liu Y. Respiratory Mucosal Immunity: Kinetics of Secretory Immunoglobulin A in Sputum and Throat Swabs From COVID-19 Patients and Vaccine Recipients. Front Microbiol 2022; 13:782421. [PMID: 35283823 PMCID: PMC8914317 DOI: 10.3389/fmicb.2022.782421] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2021] [Accepted: 01/03/2022] [Indexed: 11/13/2022] Open
Abstract
While IgM and IgG response to SARS-CoV-2 has been extensively studied, relatively little is known about secretory IgA (sIgA) response in respiratory mucosa. Here we report IgA response to the SARS-CoV-2 in sputum, throat swabs, and serum with nucleocapsid protein (NP) enzyme-linked immunosorbent assays (ELISA) in a cohort of 28 COVID-19 patients and 55 vaccine recipients. The assays showed sIgA in respiratory mucosa could be detected on the first day after illness onset (AIO), and the median conversion time for sIgA in sputum, throat swabs, and serum was 3, 4, and 10 days, respectively. The positive rates of sIgA first week AIO were 100% (24/28) and 85.7% (24/28) in sputum and throat swabs, respectively, and were both 100% during the mid-onset (2–3 weeks AIO). During the recovery period, sIgA positive rates in sputum and throat swabs gradually decreased from 60.7% (17/28) and 57.1% (16/28) 1 month AIO and the sIgA antibodies were all undetectable 6 months AIO. However, serum IgA positive rate was still 100% at 4 months and 53.6% (15/28) at 6 months. Throat swabs obtained from volunteers who received inactivated SARS-CoV-2 vaccines by intramuscular delivery all showed negative results in IgA ELISA. These findings will likely improve our understanding of respiratory mucosal immunity of this emerging disease and help in containing the pandemic and developing vaccines.
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Affiliation(s)
- Cuiping Ren
- Department of Microbiology and Parasitology, Anhui Medical University, Hefei, China
- Anhui Provincial Laboratory of Pathogen Biology, Anhui Medical University, Hefei, China
- Anhui Key Laboratory of Zoonosis of High Institution, Anhui Medical University, Hefei, China
- Laboratory of Tropical and Parasitic Diseases Control, Anhui Medical University, Hefei, China
- School of Basic Medical Sciences, Anhui Medical University, Hefei, China
| | - Yong Gao
- Department of Clinical Laboratory, The Second People’s Hospital of Fuyang, Fuyang, China
| | - Cong Zhang
- Department of Microbiology and Parasitology, Anhui Medical University, Hefei, China
- Anhui Provincial Laboratory of Pathogen Biology, Anhui Medical University, Hefei, China
- Anhui Key Laboratory of Zoonosis of High Institution, Anhui Medical University, Hefei, China
- Laboratory of Tropical and Parasitic Diseases Control, Anhui Medical University, Hefei, China
- School of Basic Medical Sciences, Anhui Medical University, Hefei, China
| | - Chang Zhou
- Department of Microbiology and Parasitology, Anhui Medical University, Hefei, China
- Anhui Provincial Laboratory of Pathogen Biology, Anhui Medical University, Hefei, China
- Anhui Key Laboratory of Zoonosis of High Institution, Anhui Medical University, Hefei, China
- Laboratory of Tropical and Parasitic Diseases Control, Anhui Medical University, Hefei, China
- School of Basic Medical Sciences, Anhui Medical University, Hefei, China
| | - Ying Hong
- Maanshan Center for Disease Control and Prevention, Maanshan, China
| | - Mingsheng Qu
- Department of Microbiology and Parasitology, Anhui Medical University, Hefei, China
- Anhui Provincial Laboratory of Pathogen Biology, Anhui Medical University, Hefei, China
- Anhui Key Laboratory of Zoonosis of High Institution, Anhui Medical University, Hefei, China
- Laboratory of Tropical and Parasitic Diseases Control, Anhui Medical University, Hefei, China
- School of Basic Medical Sciences, Anhui Medical University, Hefei, China
| | - Zhirong Zhao
- Maanshan Center for Disease Control and Prevention, Maanshan, China
| | - Yinan Du
- Department of Microbiology and Parasitology, Anhui Medical University, Hefei, China
- Anhui Provincial Laboratory of Pathogen Biology, Anhui Medical University, Hefei, China
- Anhui Key Laboratory of Zoonosis of High Institution, Anhui Medical University, Hefei, China
- Laboratory of Tropical and Parasitic Diseases Control, Anhui Medical University, Hefei, China
- School of Basic Medical Sciences, Anhui Medical University, Hefei, China
| | - Li Yang
- Department of Microbiology and Parasitology, Anhui Medical University, Hefei, China
- Anhui Provincial Laboratory of Pathogen Biology, Anhui Medical University, Hefei, China
- Anhui Key Laboratory of Zoonosis of High Institution, Anhui Medical University, Hefei, China
- Laboratory of Tropical and Parasitic Diseases Control, Anhui Medical University, Hefei, China
- School of Basic Medical Sciences, Anhui Medical University, Hefei, China
| | - Boyu Liu
- Department of Microbiology and Parasitology, Anhui Medical University, Hefei, China
- Anhui Provincial Laboratory of Pathogen Biology, Anhui Medical University, Hefei, China
- Anhui Key Laboratory of Zoonosis of High Institution, Anhui Medical University, Hefei, China
- Laboratory of Tropical and Parasitic Diseases Control, Anhui Medical University, Hefei, China
- School of Basic Medical Sciences, Anhui Medical University, Hefei, China
| | - Siying Wang
- Department of Microbiology and Parasitology, Anhui Medical University, Hefei, China
- Anhui Provincial Laboratory of Pathogen Biology, Anhui Medical University, Hefei, China
- Anhui Key Laboratory of Zoonosis of High Institution, Anhui Medical University, Hefei, China
- Laboratory of Tropical and Parasitic Diseases Control, Anhui Medical University, Hefei, China
- School of Basic Medical Sciences, Anhui Medical University, Hefei, China
| | - Mingfeng Han
- Department of Clinical Laboratory, The Second People’s Hospital of Fuyang, Fuyang, China
- *Correspondence: Mingfeng Han,
| | - Yuxian Shen
- Department of Microbiology and Parasitology, Anhui Medical University, Hefei, China
- Anhui Provincial Laboratory of Pathogen Biology, Anhui Medical University, Hefei, China
- Anhui Key Laboratory of Zoonosis of High Institution, Anhui Medical University, Hefei, China
- Laboratory of Tropical and Parasitic Diseases Control, Anhui Medical University, Hefei, China
- School of Basic Medical Sciences, Anhui Medical University, Hefei, China
- Yuxian Shen,
| | - Yan Liu
- Department of Microbiology and Parasitology, Anhui Medical University, Hefei, China
- Anhui Provincial Laboratory of Pathogen Biology, Anhui Medical University, Hefei, China
- Anhui Key Laboratory of Zoonosis of High Institution, Anhui Medical University, Hefei, China
- Laboratory of Tropical and Parasitic Diseases Control, Anhui Medical University, Hefei, China
- School of Basic Medical Sciences, Anhui Medical University, Hefei, China
- Yan Liu,
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22
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Zhuo SH, Wu JJ, Zhao L, Li WH, Zhao YF, Li YM. A chitosan-mediated inhalable nanovaccine against SARS-CoV-2. NANO RESEARCH 2022; 15:4191-4200. [PMID: 35126879 PMCID: PMC8809230 DOI: 10.1007/s12274-021-4012-9] [Citation(s) in RCA: 26] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 10/20/2021] [Revised: 11/19/2021] [Accepted: 11/22/2021] [Indexed: 06/14/2023]
Abstract
UNLABELLED Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), with several antigenic variants, has grown into a global challenge, and the rapid establishment of an immune barrier is crucial to achieving long-term control of the virus. This has led to a great demand for easy preparation and scalable vaccines, especially in low-income countries. Here, we present an inhalable nanovaccine comprising chitosan and SARS-CoV-2 spike protein. The chitosan-mediated nanovaccine enabled a strong spike-specific antibody immune response and augmented local mucosal immunity in bronchoalveolar lavage and lungs, which might be capable of protecting the host from infection without systemic toxicity. In addition, the enhanced adaptive immunity stimulated by chitosan showed potential protection against SARS-CoV-2. Furthermore, inhalation of the nanovaccine induced a comparable antibody response compared to intramuscular injection. This inhalable nanovaccine against SARS-CoV-2 offers a convenient and compliant strategy to reduce the use of needles and the need for medical staff. ELECTRONIC SUPPLEMENTARY MATERIAL Supplementary material (the immune activation of CS-mediated nanovacccine on BMDCs, cell viability, immune responses in lungs and BALF, serum chemistry and H&E histopathological analysis.) is available in the online version of this article at 10.1007/s12274-021-4012-9.
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Affiliation(s)
- Shao-Hua Zhuo
- Key Lab of Bioorganic Phosphorus Chemistry & Chemical Biology, Department of Chemistry, Tsinghua University, Beijing, 100084 China
| | - Jun-Jun Wu
- Key Lab of Bioorganic Phosphorus Chemistry & Chemical Biology, Department of Chemistry, Tsinghua University, Beijing, 100084 China
| | - Lang Zhao
- Key Lab of Bioorganic Phosphorus Chemistry & Chemical Biology, Department of Chemistry, Tsinghua University, Beijing, 100084 China
| | - Wen-Hao Li
- Key Lab of Bioorganic Phosphorus Chemistry & Chemical Biology, Department of Chemistry, Tsinghua University, Beijing, 100084 China
| | - Yu-Fen Zhao
- Key Lab of Bioorganic Phosphorus Chemistry & Chemical Biology, Department of Chemistry, Tsinghua University, Beijing, 100084 China
- Institute of Drug Discovery Technology, Ningbo University, Ningbo, 315221 China
| | - Yan-Mei Li
- Key Lab of Bioorganic Phosphorus Chemistry & Chemical Biology, Department of Chemistry, Tsinghua University, Beijing, 100084 China
- Beijing Institute for Brain Disorders, Beijing, 100069 China
- Center for Synthetic and Systems Biology, Tsinghua University, Beijing, 100084 China
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23
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Saravanan UB, Namachivayam M, Jeewon R, Huang JD, Durairajan SSK. Animal models for SARS-CoV-2 and SARS-CoV-1 pathogenesis, transmission and therapeutic evaluation. World J Virol 2022; 11:40-56. [PMID: 35117970 PMCID: PMC8788210 DOI: 10.5501/wjv.v11.i1.40] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/24/2021] [Revised: 08/22/2021] [Accepted: 11/24/2021] [Indexed: 02/06/2023] Open
Abstract
There is a critical need to develop animal models to alleviate vaccine and drug development difficulties against zoonotic viral infections. The coronavirus family, which includes severe acute respiratory syndrome coronavirus 1 and severe acute respiratory syndrome coronavirus 2, crossed the species barrier and infected humans, causing a global outbreak in the 21st century. Because humans do not have pre-existing immunity against these viral infections and with ethics governing clinical trials, animal models are therefore being used in clinical studies to facilitate drug discovery and testing efficacy of vaccines. The ideal animal models should reflect the viral replication, clinical signs, and pathological responses observed in humans. Different animal species should be tested to establish an appropriate animal model to study the disease pathology, transmission and evaluation of novel vaccine and drug candidates to treat coronavirus disease 2019. In this context, the present review summarizes the recent progress in developing animal models for these two pathogenic viruses and highlights the utility of these models in studying SARS-associated coronavirus diseases.
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Affiliation(s)
- Udhaya Bharathy Saravanan
- Department of Microbiology, School of Life Sciences, Central University of Tamil Nadu, Tiruvarur 610005, India
| | - Mayurikaa Namachivayam
- Department of Microbiology, School of Life Sciences, Central University of Tamil Nadu, Tiruvarur 610005, India
| | - Rajesh Jeewon
- Department of Health Sciences, Faculty of Medicine and Health Sciences, University of Mauritius, Reduit 80837, Mauritius
| | - Jian-Dong Huang
- School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong, China
- CAS Key Laboratory of Quantitative Engineering Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, Guangdong Province, China
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24
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Chung DR. Responses against infectious disease pandemics: a narrative review on COVID-19. PRECISION AND FUTURE MEDICINE 2021. [DOI: 10.23838/pfm.2021.00156] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022] Open
Abstract
Currently, the world is facing the coronavirus disease 2019 (COVID-19) pandemic. With this, an emerging infectious disease pandemic in the absence of effective antiviral agents and vaccines for a novel virus is no different from the 1918 influenza pandemic, which became a great disaster for humankind. We also experienced a global lockdown with a stringent implementation of social distancing, which is a first for mankind living in the present day, and has led to enormous economic damage and restrictions on individual freedom. The microorganism that will cause the next pandemic may be a highly fatal avian influenza virus, another coronavirus, or a completely different microorganism. This COVID-19 pandemic is an enormous lesson for humankind and is tantamount to a vaccine in preparation for the next pandemic. Important and urgent undertakings were given to each country in terms of complementing laws and regulations for a stronger and more resilient healthcare system, such as investment in research and development for new rapid diagnostic technologies, vaccines, new therapeutic agents, among others.
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25
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Del Fresno C, García-Arriaza J, Martínez-Cano S, Heras-Murillo I, Jarit-Cabanillas A, Amores-Iniesta J, Brandi P, Dunphy G, Suay-Corredera C, Pricolo MR, Vicente N, López-Perrote A, Cabezudo S, González-Corpas A, Llorca O, Alegre-Cebollada J, Garaigorta U, Gastaminza P, Esteban M, Sancho D. The Bacterial Mucosal Immunotherapy MV130 Protects Against SARS-CoV-2 Infection and Improves COVID-19 Vaccines Immunogenicity. Front Immunol 2021; 12:748103. [PMID: 34867974 PMCID: PMC8637175 DOI: 10.3389/fimmu.2021.748103] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2021] [Accepted: 10/25/2021] [Indexed: 12/17/2022] Open
Abstract
COVID-19-specific vaccines are efficient prophylactic weapons against SARS-CoV-2 virus. However, boosting innate responses may represent an innovative way to immediately fight future emerging viral infections or boost vaccines. MV130 is a mucosal immunotherapy, based on a mixture of whole heat-inactivated bacteria, that has shown clinical efficacy against recurrent viral respiratory infections. Herein, we show that the prophylactic intranasal administration of this immunotherapy confers heterologous protection against SARS-CoV-2 infection in susceptible K18-hACE2 mice. Furthermore, in C57BL/6 mice, prophylactic administration of MV130 improves the immunogenicity of two different COVID-19 vaccine formulations targeting the SARS-CoV-2 spike (S) protein, inoculated either intramuscularly or intranasally. Independently of the vaccine candidate and vaccination route used, intranasal prophylaxis with MV130 boosted S-specific responses, including CD8+-T cell activation and the production of S-specific mucosal IgA antibodies. Therefore, the bacterial mucosal immunotherapy MV130 protects against SARS-CoV-2 infection and improves COVID-19 vaccines immunogenicity.
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Affiliation(s)
- Carlos Del Fresno
- Department of Myocardial Pathophysiology, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain.,Department of Infectious Diseases and Immunity, Instituto de Investigación Biomédica del Hospital Universitario la Paz (IdiPAZ), Madrid, Spain
| | - Juan García-Arriaza
- Department of Molecular and Cellular Biology, Centro Nacional de Biotecnología (CNB), Consejo Superior de Investigaciones Científicas (CSIC), Madrid, Spain
| | - Sarai Martínez-Cano
- Department of Myocardial Pathophysiology, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain.,R&D Department, Inmunotek S.L., Alcalá de Henares, Spain
| | - Ignacio Heras-Murillo
- Department of Myocardial Pathophysiology, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain
| | - Aitor Jarit-Cabanillas
- Department of Myocardial Pathophysiology, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain
| | - Joaquín Amores-Iniesta
- Department of Myocardial Pathophysiology, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain
| | - Paola Brandi
- Department of Myocardial Pathophysiology, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain
| | - Gillian Dunphy
- Department of Myocardial Pathophysiology, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain
| | - Carmen Suay-Corredera
- Department of Myocardial Pathophysiology, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain
| | - Maria Rosaria Pricolo
- Department of Myocardial Pathophysiology, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain
| | - Natalia Vicente
- Department of Myocardial Pathophysiology, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain
| | - Andrés López-Perrote
- Structural Biology Department, Centro Nacional de Investigaciones Oncológicas (CNIO), Madrid, Spain
| | - Sofía Cabezudo
- Structural Biology Department, Centro Nacional de Investigaciones Oncológicas (CNIO), Madrid, Spain
| | - Ana González-Corpas
- Structural Biology Department, Centro Nacional de Investigaciones Oncológicas (CNIO), Madrid, Spain
| | - Oscar Llorca
- Structural Biology Department, Centro Nacional de Investigaciones Oncológicas (CNIO), Madrid, Spain
| | - Jorge Alegre-Cebollada
- Department of Myocardial Pathophysiology, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain
| | - Urtzi Garaigorta
- Department of Molecular and Cellular Biology, Centro Nacional de Biotecnología (CNB), Consejo Superior de Investigaciones Científicas (CSIC), Madrid, Spain
| | - Pablo Gastaminza
- Department of Molecular and Cellular Biology, Centro Nacional de Biotecnología (CNB), Consejo Superior de Investigaciones Científicas (CSIC), Madrid, Spain
| | - Mariano Esteban
- Department of Molecular and Cellular Biology, Centro Nacional de Biotecnología (CNB), Consejo Superior de Investigaciones Científicas (CSIC), Madrid, Spain
| | - David Sancho
- Department of Myocardial Pathophysiology, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain
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Lapuente D, Fuchs J, Willar J, Vieira Antão A, Eberlein V, Uhlig N, Issmail L, Schmidt A, Oltmanns F, Peter AS, Mueller-Schmucker S, Irrgang P, Fraedrich K, Cara A, Hoffmann M, Pöhlmann S, Ensser A, Pertl C, Willert T, Thirion C, Grunwald T, Überla K, Tenbusch M. Protective mucosal immunity against SARS-CoV-2 after heterologous systemic prime-mucosal boost immunization. Nat Commun 2021; 12:6871. [PMID: 34836955 PMCID: PMC8626513 DOI: 10.1038/s41467-021-27063-4] [Citation(s) in RCA: 149] [Impact Index Per Article: 37.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2021] [Accepted: 11/01/2021] [Indexed: 01/02/2023] Open
Abstract
Several effective SARS-CoV-2 vaccines are currently in use, but effective boosters are needed to maintain or increase immunity due to waning responses and the emergence of novel variants. Here we report that intranasal vaccinations with adenovirus 5 and 19a vectored vaccines following a systemic plasmid DNA or mRNA priming result in systemic and mucosal immunity in mice. In contrast to two intramuscular applications of an mRNA vaccine, intranasal boosts with adenoviral vectors induce high levels of mucosal IgA and lung-resident memory T cells (TRM); mucosal neutralization of virus variants of concern is also enhanced. The mRNA prime provokes a comprehensive T cell response consisting of circulating and lung TRM after the boost, while the plasmid DNA prime induces mostly mucosal T cells. Concomitantly, the intranasal boost strategies lead to complete protection against a SARS-CoV-2 infection in mice. Our data thus suggest that mucosal booster immunizations after mRNA priming is a promising approach to establish mucosal immunity in addition to systemic responses.
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Affiliation(s)
- Dennis Lapuente
- Institute of Clinical and Molecular Virology, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nürnberg, Erlangen, Germany.
| | - Jana Fuchs
- Institute of Clinical and Molecular Virology, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nürnberg, Erlangen, Germany
| | - Jonas Willar
- Institute of Clinical and Molecular Virology, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nürnberg, Erlangen, Germany
| | - Ana Vieira Antão
- Institute of Clinical and Molecular Virology, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nürnberg, Erlangen, Germany
| | - Valentina Eberlein
- Department of Immunology, Fraunhofer Institute for Cell Therapy and Immunology, IZI, Leipzig, Germany
- Fraunhofer Cluster of Excellence Immune-mediated Diseases CIMD, Frankfurt am Main, Germany
| | - Nadja Uhlig
- Department of Immunology, Fraunhofer Institute for Cell Therapy and Immunology, IZI, Leipzig, Germany
- Fraunhofer Cluster of Excellence Immune-mediated Diseases CIMD, Frankfurt am Main, Germany
| | - Leila Issmail
- Department of Immunology, Fraunhofer Institute for Cell Therapy and Immunology, IZI, Leipzig, Germany
- Fraunhofer Cluster of Excellence Immune-mediated Diseases CIMD, Frankfurt am Main, Germany
| | - Anna Schmidt
- Institute of Clinical and Molecular Virology, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nürnberg, Erlangen, Germany
| | - Friederike Oltmanns
- Institute of Clinical and Molecular Virology, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nürnberg, Erlangen, Germany
| | - Antonia Sophia Peter
- Institute of Clinical and Molecular Virology, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nürnberg, Erlangen, Germany
| | - Sandra Mueller-Schmucker
- Institute of Clinical and Molecular Virology, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nürnberg, Erlangen, Germany
| | - Pascal Irrgang
- Institute of Clinical and Molecular Virology, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nürnberg, Erlangen, Germany
| | - Kirsten Fraedrich
- Institute of Clinical and Molecular Virology, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nürnberg, Erlangen, Germany
| | - Andrea Cara
- National Center for Global Health, Istituto Superiore di Sanità, Rome, Italy
| | - Markus Hoffmann
- Infection Biology Unit, German Primate Center-Leibniz Institute for Primate Research, Göttingen, Germany
- Faculty of Biology and Psychology, Georg-August-University Göttingen, Göttingen, Germany
| | - Stefan Pöhlmann
- Infection Biology Unit, German Primate Center-Leibniz Institute for Primate Research, Göttingen, Germany
- Faculty of Biology and Psychology, Georg-August-University Göttingen, Göttingen, Germany
| | - Armin Ensser
- Institute of Clinical and Molecular Virology, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nürnberg, Erlangen, Germany
| | | | | | | | - Thomas Grunwald
- Department of Immunology, Fraunhofer Institute for Cell Therapy and Immunology, IZI, Leipzig, Germany
- Fraunhofer Cluster of Excellence Immune-mediated Diseases CIMD, Frankfurt am Main, Germany
| | - Klaus Überla
- Institute of Clinical and Molecular Virology, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nürnberg, Erlangen, Germany
| | - Matthias Tenbusch
- Institute of Clinical and Molecular Virology, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nürnberg, Erlangen, Germany.
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Garcia-Pelagio KP, Hew-Butler T, Fahlman MM, Roche JA. Women's Lives Matter-The Critical Need for Women to Prioritize Optimal Physical Activity to Reduce COVID-19 Illness Risk and Severity. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2021; 18:10271. [PMID: 34639569 PMCID: PMC8507774 DOI: 10.3390/ijerph181910271] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/04/2021] [Revised: 09/21/2021] [Accepted: 09/22/2021] [Indexed: 01/08/2023]
Abstract
Physical activity (PA) is beneficial for the health and wellness of individuals and societies. During an infectious disease pandemic, such as the one caused by COVID-19, social distancing, quarantines, and lockdowns are used to reduce community spread of the disease. Unfortunately, such nonpharmacological interventions or physical risk mitigation measures also make it challenging to engage in PA. Reduced PA could then trigger physiological changes that affect both mental and physical health. In this regard, women are more likely to experience physical and psychological distress. PA is a safe and effective nonpharmacological modality that can help prevent and manage several mental and physical health problems when performed correctly. PA might even confer benefits that are directly related to decreasing COVID-19 morbidity and mortality in women. In this review, we summarize why optimal PA must be a priority for women during the COVID-19 pandemic. We then discuss chronic COVID-19 illness and its impact on women, which further underscores the need for worldwide preventive health strategies that include PA. Finally, we discuss the importance of vaccination against COVID-19 for women, as part of prioritizing preventive healthcare and an active lifestyle.
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Affiliation(s)
- Karla P. Garcia-Pelagio
- Departamento de Física, Facultad de Ciencias, Universidad Nacional Autónoma de México, Ciudad de México 4510, Mexico
| | - Tamara Hew-Butler
- Division of Kinesiology, Health and Sport Studies, College of Education, Wayne State University, Detroit, MI 48201, USA; (T.H.-B.); (M.M.F.)
| | - Mariane M. Fahlman
- Division of Kinesiology, Health and Sport Studies, College of Education, Wayne State University, Detroit, MI 48201, USA; (T.H.-B.); (M.M.F.)
| | - Joseph A. Roche
- Physical Therapy Program, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, Detroit, MI 48201, USA
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28
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Discontinuation of Transmission Precautions for COVID-19 Patients: Polymerase Chain Reaction Diagnostics, Patient Delays, and Cycle Threshold Values. ACTA ACUST UNITED AC 2021; 29:e287-e293. [PMID: 34539163 PMCID: PMC8436810 DOI: 10.1097/ipc.0000000000001005] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
Background The decision of when it is safe to discontinue transmission-based precautions for SARS-CoV-2 coronavirus disease 2019 (COVID-19) hospitalized patients has been controversial. The Centers for Disease Control and Prevention offered reverse transcriptase polymerase chain reaction (PCR) diagnostic test- or symptom-based guidelines. Methods A retrospective chart review of Vidant Health system, Eastern North Carolina, was conducted. Length of stay, days in isolation unit, and date appropriate for discharge or isolation discontinuation based on the symptom-based strategy were recorded. Results Of 196 COVID hospitalized patients, 34 had repeated COVID PCR tests 3 or more days from their first positive test result. Half of these patients experienced delays in release from transmission-based precautions because of repeated positive PCR test results and use of the test-based approach. This resulted in an additional 166 days of hospitalization, costing an estimated $415,000. Furthermore, 2 subjects had a combined 16-day delay in necessary medical procedures. Most of the COVID PCR platforms yield quantitative results in the form of cycle threshold (Ct) values, the number of cycles needed to detect the genome. These values have also been used to assess whether patients are likely to remain contagious. None of our patients who met the criteria for symptom-based strategy for transmission-based precaution discontinuation had positive PCR test results with Ct values lower than 25, but 4 had Ct values lower than 30. Conclusions Concerns surround immunocompromised patients and those treated with steroids who might be delayed or incapable of stopping viral replication and thus remain contagious. Our results suggest that clinicians use all available data including Ct values to evaluate the safety of discontinuation of transmission precautions.
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29
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Hamorsky KT, Bushau-Sprinkle AM, Kitterman K, Corman JM, DeMarco J, Keith RJ, Bhatnagar A, Fuqua JL, Lasnik A, Joh J, Chung D, Klein J, Flynn J, Gardner M, Barve S, Ghare SS, Palmer KE. Serological assessment of SARS-CoV-2 infection during the first wave of the pandemic in Louisville Kentucky. Sci Rep 2021; 11:18285. [PMID: 34521900 PMCID: PMC8440627 DOI: 10.1038/s41598-021-97423-z] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2021] [Accepted: 08/09/2021] [Indexed: 12/13/2022] Open
Abstract
Serological assays intended for diagnosis, sero-epidemiologic assessment, and measurement of protective antibody titers upon infection or vaccination are essential for managing the SARS-CoV-2 pandemic. Serological assays measuring the antibody responses against SARS-CoV-2 antigens are readily available. However, some lack appropriate characteristics to accurately measure SARS-CoV-2 antibodies titers and neutralization. We developed an Enzyme-linked Immunosorbent Assay (ELISA) methods for measuring IgG, IgA, and IgM responses to SARS-CoV-2, Spike (S), receptor binding domain (RBD), and nucleocapsid (N) proteins. Performance characteristics of sensitivity and specificity have been defined. ELISA results show positive correlation with microneutralization and Plaque Reduction Neutralization assays with infectious SARS-CoV-2. Our ELISA was used to screen healthcare workers in Louisville, KY during the first wave of the local pandemic in the months of May and July 2020. We found a seropositive rate of approximately 1.4% and 2.3%, respectively. Our analyses demonstrate a broad immune response among individuals and suggest some non-RBD specific S IgG and IgA antibodies neutralize SARS-CoV-2.
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Affiliation(s)
- Krystal T Hamorsky
- James Graham Brown Cancer Center, University of Louisville School of Medicine, University of Louisville, Louisville, KY, USA.
- Center for Predictive Medicine for Biodefense and Emerging Infectious Diseases, University of Louisville School of Medicine, University of Louisville, Louisville, KY, USA.
- Department of Medicine, University of Louisville School of Medicine, University of Louisville, Louisville, KY, USA.
| | - Adrienne M Bushau-Sprinkle
- Center for Predictive Medicine for Biodefense and Emerging Infectious Diseases, University of Louisville School of Medicine, University of Louisville, Louisville, KY, USA
- Department of Medicine, University of Louisville School of Medicine, University of Louisville, Louisville, KY, USA
| | - Kathleen Kitterman
- Center for Predictive Medicine for Biodefense and Emerging Infectious Diseases, University of Louisville School of Medicine, University of Louisville, Louisville, KY, USA
- Department of Medicine, University of Louisville School of Medicine, University of Louisville, Louisville, KY, USA
| | - Julia M Corman
- Center for Predictive Medicine for Biodefense and Emerging Infectious Diseases, University of Louisville School of Medicine, University of Louisville, Louisville, KY, USA
| | - Jennifer DeMarco
- Center for Predictive Medicine for Biodefense and Emerging Infectious Diseases, University of Louisville School of Medicine, University of Louisville, Louisville, KY, USA
- Department of Microbiology and Immunology, University of Louisville School of Medicine, University of Louisville, Louisville, KY, USA
| | - Rachel J Keith
- Christine Lee Brown Envirome Institute, University of Louisville School of Medicine, University of Louisville, Louisville, KY, USA
- Diabetes and Obesity Center, University of Louisville School of Medicine, University of Louisville, Louisville, KY, USA
| | - Aruni Bhatnagar
- Christine Lee Brown Envirome Institute, University of Louisville School of Medicine, University of Louisville, Louisville, KY, USA
- Diabetes and Obesity Center, University of Louisville School of Medicine, University of Louisville, Louisville, KY, USA
| | - Joshua L Fuqua
- James Graham Brown Cancer Center, University of Louisville School of Medicine, University of Louisville, Louisville, KY, USA
- Center for Predictive Medicine for Biodefense and Emerging Infectious Diseases, University of Louisville School of Medicine, University of Louisville, Louisville, KY, USA
- Department of Pharmacology and Toxicology, University of Louisville School of Medicine, University of Louisville, Louisville, KY, USA
| | - Amanda Lasnik
- James Graham Brown Cancer Center, University of Louisville School of Medicine, University of Louisville, Louisville, KY, USA
- Center for Predictive Medicine for Biodefense and Emerging Infectious Diseases, University of Louisville School of Medicine, University of Louisville, Louisville, KY, USA
- Department of Pharmacology and Toxicology, University of Louisville School of Medicine, University of Louisville, Louisville, KY, USA
| | - Joongho Joh
- James Graham Brown Cancer Center, University of Louisville School of Medicine, University of Louisville, Louisville, KY, USA
- Department of Medicine, University of Louisville School of Medicine, University of Louisville, Louisville, KY, USA
| | - Donghoon Chung
- Center for Predictive Medicine for Biodefense and Emerging Infectious Diseases, University of Louisville School of Medicine, University of Louisville, Louisville, KY, USA
- Department of Microbiology and Immunology, University of Louisville School of Medicine, University of Louisville, Louisville, KY, USA
| | - Jon Klein
- Department of Medicine, University of Louisville School of Medicine, University of Louisville, Louisville, KY, USA
| | - Joseph Flynn
- Norton Cancer Institute, Norton Healthcare, Louisville, KY, USA
| | - Marti Gardner
- Norton Cancer Institute, Norton Healthcare, Louisville, KY, USA
| | - Shirish Barve
- Department of Medicine, University of Louisville School of Medicine, University of Louisville, Louisville, KY, USA
- Department of Pharmacology and Toxicology, University of Louisville School of Medicine, University of Louisville, Louisville, KY, USA
- Alcohol Research Center, University of Louisville School of Medicine, University of Louisville, Louisville, KY, USA
| | - Smita S Ghare
- Department of Medicine, University of Louisville School of Medicine, University of Louisville, Louisville, KY, USA
- Alcohol Research Center, University of Louisville School of Medicine, University of Louisville, Louisville, KY, USA
| | - Kenneth E Palmer
- James Graham Brown Cancer Center, University of Louisville School of Medicine, University of Louisville, Louisville, KY, USA
- Center for Predictive Medicine for Biodefense and Emerging Infectious Diseases, University of Louisville School of Medicine, University of Louisville, Louisville, KY, USA
- Department of Pharmacology and Toxicology, University of Louisville School of Medicine, University of Louisville, Louisville, KY, USA
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30
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Gupta D, Parthasarathy H, Sah V, Tandel D, Vedagiri D, Reddy S, Harshan KH. Inactivation of SARS-CoV-2 by β-propiolactone causes aggregation of viral particles and loss of antigenic potential. Virus Res 2021; 305:198555. [PMID: 34487766 PMCID: PMC8416322 DOI: 10.1016/j.virusres.2021.198555] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2021] [Revised: 08/24/2021] [Accepted: 08/26/2021] [Indexed: 12/19/2022]
Abstract
Inactivated viral preparations are important resources in vaccine and antisera industry. Of the many vaccines that are being developed against COVID-19, inactivated whole-virus vaccines are also considered effective. β-propiolactone (BPL) is a widely used chemical inactivator of several viruses. Here, we analyze various concentrations of BPL to effectively inactivate SARS-CoV-2 and their effects on the biochemical properties of the virion particles. BPL at 1:2000 (v/v) concentrations effectively inactivated SARS-CoV-2. However, higher BPL concentrations resulted in the loss of both protein content as well as the antigenic integrity of the structural proteins. Higher concentrations also caused substantial aggregation of the virion particles possibly resulting in insufficient inactivation, and a loss in antigenic potential. We also identify that the viral RNA content in the culture supernatants can be a direct indicator of their antigenic content. Our findings may have important implications in the vaccine and antisera industry during COVID-19 pandemic.
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Affiliation(s)
- Divya Gupta
- Centre for Cellular and Molecular Biology, Hyderabad 500007, India
| | | | - Vishal Sah
- Centre for Cellular and Molecular Biology, Hyderabad 500007, India; Academy for Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India
| | - Dixit Tandel
- Centre for Cellular and Molecular Biology, Hyderabad 500007, India; Academy for Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India
| | - Dhiviya Vedagiri
- Centre for Cellular and Molecular Biology, Hyderabad 500007, India; Academy for Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India
| | - Shashikala Reddy
- Department of Microbiology, Osmania Medical College, Koti, Hyderabad 500095, Telangana, India
| | - Krishnan H Harshan
- Centre for Cellular and Molecular Biology, Hyderabad 500007, India; Academy for Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India.
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Vila Muntadas M, Agustí Sunyer I, Agustí Garcia-Navarro A. [COVID-19 diagnostic tests: importance of the clinical context]. Med Clin (Barc) 2021; 157:185-190. [PMID: 34158178 PMCID: PMC8101797 DOI: 10.1016/j.medcli.2021.03.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2020] [Revised: 03/10/2021] [Accepted: 03/12/2021] [Indexed: 11/16/2022]
Abstract
The current SARS-CoV-2 pandemic poses numerous health challenges, including the adequate use and proper interpretation of the different available tests in different clinical settings. As any diagnostic test, those of SARS-CoV-2 have methodological limitations of sensitivity (S) and specificity (E), which eventually determine their positive (PPV) and negative (NPV) predictive value. Furthermore, their diagnostic performance depends on the clinical context in which these tests are used, that is, on the pretest probability. This article: (1) reviews the main methodological aspects that influence the S, E, PPV and NPV of the most common SARS-CoV-2 diagnostic tests; and, (2) discusses its diagnostic interpretation in different clinical settings.
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Affiliation(s)
| | | | - Alvar Agustí Garcia-Navarro
- Hospital Clínic de Barcelona, Barcelona, España; Universidad de Barcelona (UB), Barcelona, España; CIBER Enfermedades Respiratorias, Madrid, España
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32
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Vila Muntadas M, Agustí Sunyer I, Agustí Garcia-Navarro A. COVID-19 diagnostic tests: Importance of the clinical context. MEDICINA CLINICA (ENGLISH ED.) 2021; 157:185-190. [PMID: 34368460 PMCID: PMC8324468 DOI: 10.1016/j.medcle.2021.03.008] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 12/10/2020] [Accepted: 03/12/2021] [Indexed: 12/24/2022]
Abstract
The current SARS-CoV-2 pandemic poses numerous health challenges, including the adequate use and proper interpretation of the different available tests in different clinical settings. As any diagnostic test, those of SARS-CoV-2 have methodological limitations of sensitivity (S) and specificity (E), which eventually determine their positive (PPV) and negative (NPV) predictive value. Furthermore, their diagnostic performance depends on the clinical context in which these tests are used, that is, on the pretest probability. This article: (1) reviews the main methodological aspects that influence the S, E, PPV and NPV of the most common SARS-CoV-2 diagnostic tests; and, (2) discusses its diagnostic interpretation in different clinical settings.
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Affiliation(s)
| | | | - Alvar Agustí Garcia-Navarro
- Hospital Clínic de Barcelona, Barcelona, Spain
- Universidad de Barcelona (UB), Barcelona, Spain
- CIBER Enfermedades Respiratorias, Madrid, Spain
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33
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Saleh AA, Saad MA, Ryan I, Amin M, Shindy MI, Hassan WA, Samir M, Khattab AA, Abdelgayed SS, Seadawy MG, Fahmy HM, Amer K. Safety and immunogenicity evaluation of inactivated whole-virus-SARS-COV-2 as emerging vaccine development in Egypt. Antib Ther 2021; 4:135-143. [PMID: 34286215 PMCID: PMC8287638 DOI: 10.1093/abt/tbab012] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2021] [Revised: 05/26/2021] [Accepted: 06/21/2021] [Indexed: 12/23/2022] Open
Abstract
BACKGROUND Current worldwide pandemic coronavirus disease 2019 (COVID-19) with high numbers of mortality rates and huge economic problems require an urgent demand for safe and effective vaccine development. Inactivated SARS-CoV2 vaccine with alum. Hydroxide can play an important role in reducing the impacts of the COVID-19 pandemic. In this study, vaccine efficacy was evaluated through the detection of the neutralizing antibodies that protect mice from challenge with SARS-CoV 2 3 weeks after the second dose. We conclude that the vaccine described here has safety and desirable properties, and our data support further development and plans for clinical trials. METHODS Characterized SARS-COV-2 strain, severe acute respiratory syndrome coronavirus 2 isolates (SARS-CoV-2/human/EGY/Egy-SERVAC/2020) with accession numbers; MT981440; MT981439; MT981441; MT974071; MT974069; and MW250352 at GenBank were isolated from Egyptian patients SARS-CoV-2-positive. Development of inactivated vaccine was carried out in a BSL-3 facilities and the immunogenicity was determined in mice at two doses (55 and 100 μg per dose). RESULTS The distinct cytopathic effect induced by SARS-COV-2 propagation on Vero cell monolayers and the viral particles were identified as Coronaviridae by transmission electron microscopy and RT-PCR on infected cells cultures. Immunogenicity of the developed vaccine indicated the high antigen-binding and neutralizing antibody titers, regardless of the dose concentration, with excellent safety profiles and no deaths or clinical symptoms in mice groups. The efficacy of the inactivated vaccine formulation was tested by the wild virus challenge of the vaccinated mice and viral replication detection in lung tissues. CONCLUSIONS Vaccinated mice recorded complete protection from challenge infection via inhibition of SARS-COV-2 replication in the lung tissues of mice following virus challenge, regardless of the level of serum neutralizing antibodies. This finding will support future trials for the evaluation of an applicable SARS-CoV-2 vaccine candidate.
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Affiliation(s)
- Amani A Saleh
- A.R.C. Veterinary Serum Vaccine Research Institute (VSVRI), 131 El-Sekka El-Bidaa st. Cairo 11384, Egypt
| | - Mohamed A Saad
- A.R.C. Veterinary Serum Vaccine Research Institute (VSVRI), 131 El-Sekka El-Bidaa st. Cairo 11384, Egypt
| | - Islam Ryan
- Egyptian Army Veterinary Corps, NR Nassar City, Cairo 11765, Egypt
| | - Magdy Amin
- Military Medical Services, Kobry El Qubba. Cairo 11766, Egypt
| | - Mohamed I Shindy
- Egyptian Army Veterinary Corps, NR Nassar City, Cairo 11765, Egypt
| | - Wael A Hassan
- Egypt Center for Research and Regenerative Medicine, 3A Ramses Extension st. Cairo, 11759, Egypt
| | - Mahmoud Samir
- Egypt Center for Research and Regenerative Medicine, 3A Ramses Extension st. Cairo, 11759, Egypt
| | - Ayman A Khattab
- Egypt Center for Research and Regenerative Medicine, 3A Ramses Extension st. Cairo, 11759, Egypt
| | - Sherein S Abdelgayed
- Department of pathology, Faculty of Veterinary Medicine, Cairo University, Giza 12211, Egypt
| | | | - Hossam M Fahmy
- Faculty of Medicine, Ain Shams University, Abbasia, Cairo 11591, Egypt
| | - Khaled Amer
- Egypt Center for Research and Regenerative Medicine, 3A Ramses Extension st. Cairo, 11759, Egypt
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34
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Annas S, Zamri-Saad M. Intranasal Vaccination Strategy to Control the COVID-19 Pandemic from a Veterinary Medicine Perspective. Animals (Basel) 2021; 11:ani11071876. [PMID: 34202429 PMCID: PMC8300178 DOI: 10.3390/ani11071876] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2021] [Revised: 06/16/2021] [Accepted: 06/21/2021] [Indexed: 12/14/2022] Open
Abstract
Simple Summary Intranasal vaccination is one of the methods used to stimulate mucosal immunity. It has been widely practised to control many human and animal respiratory diseases. Coronavirus disease 2019 (COVID-19) is a highly contagious respiratory disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which resulted in a global pandemic. COVID-19 has reminded some veterinarians of various contagious veterinary diseases, including coronavirus infections in animals. This article discusses the control of highly contagious diseases of veterinary importance with emphasis on an intranasal vaccination approach, and the potential of implementing similar strategies in human medicine to control the ongoing COVID-19 pandemic. Abstract The world is currently facing an ongoing coronavirus disease 2019 (COVID-19) pandemic. The disease is a highly contagious respiratory disease which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Current control measures used by many countries include social distancing, wearing face masks, frequent hand washing, self-isolation, and vaccination. The current commercially available vaccines are injectable vaccines, although a few intranasal vaccines are in trial stages. The reported side effects of COVID-19 vaccines, perceptions towards the safety of the vaccines, and frequent mutation of the virus may lead to poor herd immunity. In veterinary medicine, attaining herd immunity is one of the main considerations in disease control, and herd immunity depends on the use of efficacious vaccines and the vaccination coverage in a population. Hence, many aerosol or intranasal vaccines have been developed to control veterinary respiratory diseases such as Newcastle disease, rinderpest, infectious bronchitis, and haemorrhagic septicaemia. Different vaccine technologies could be employed to improve vaccination coverage, including the usage of an intranasal live recombinant vaccine or live mutant vaccine. This paper discusses the potential use of intranasal vaccination strategies against human COVID-19, based on a veterinary intranasal vaccine strategy.
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Vashishtha VM, Kumar P. Development of SARS-CoV-2 vaccines: challenges, risks, and the way forward. Hum Vaccin Immunother 2021; 17:1635-1649. [PMID: 33270478 PMCID: PMC7754925 DOI: 10.1080/21645515.2020.1845524] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2020] [Revised: 10/25/2020] [Accepted: 10/29/2020] [Indexed: 01/13/2023] Open
Abstract
The COVID-19 pandemic mandates the development of a safe and effective Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) vaccine. This review analyzes the complexities, challenges, and other vital issues associated with the development of the SARS-CoV-2 vaccine. A brief review of the immune responses (innate, antibody, and T-cell) to SARS-CoV-2, including immune targets, correlates of protection, and duration of immunity is presented. Approaches to vaccine development including different vaccine platforms, critical attributes of novel vaccine candidates, the status of the ongoing clinical trials, and the ways to speed up vaccine development are also reviewed. Despite a historical average success rate of only 6%, and a usual gestation period of 10-12 years for the development of a new vaccine, the world is on the verge of developing COVID-19 vaccines in an extraordinary short time span.
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Affiliation(s)
- Vipin M. Vashishtha
- Department of Pediatrics, Mangla Hospital & Research Center, Shakti Chowk, Bijnor, India
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36
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Li Y, Tenchov R, Smoot J, Liu C, Watkins S, Zhou Q. A Comprehensive Review of the Global Efforts on COVID-19 Vaccine Development. ACS CENTRAL SCIENCE 2021; 7:512-533. [PMID: 34056083 PMCID: PMC8029445 DOI: 10.1021/acscentsci.1c00120] [Citation(s) in RCA: 198] [Impact Index Per Article: 49.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/20/2023]
Abstract
This report examines various vaccine platforms including inactivated vaccines, protein-based vaccines, viral vector vaccines, and nucleic acid (DNA or mRNA) vaccines, and their ways of producing immunogens in cells.
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Affiliation(s)
| | | | - Jeffrey Smoot
- CAS, a division of the American Chemical Society, 2540 Olentangy River Road, Columbus, Ohio 43210-3012, United States
| | - Cynthia Liu
- CAS, a division of the American Chemical Society, 2540 Olentangy River Road, Columbus, Ohio 43210-3012, United States
| | - Steven Watkins
- CAS, a division of the American Chemical Society, 2540 Olentangy River Road, Columbus, Ohio 43210-3012, United States
| | - Qiongqiong Zhou
- CAS, a division of the American Chemical Society, 2540 Olentangy River Road, Columbus, Ohio 43210-3012, United States
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Zhang Y, Gargan S, Lu Y, Stevenson NJ. An Overview of Current Knowledge of Deadly CoVs and Their Interface with Innate Immunity. Viruses 2021; 13:560. [PMID: 33810391 PMCID: PMC8066579 DOI: 10.3390/v13040560] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2021] [Revised: 03/12/2021] [Accepted: 03/16/2021] [Indexed: 02/06/2023] Open
Abstract
Coronaviruses are a large family of zoonotic RNA viruses, whose infection can lead to mild or lethal respiratory tract disease. Severe Acute Respiratory Syndrome-Coronavirus-1 (SARS-CoV-1) first emerged in Guangdong, China in 2002 and spread to 29 countries, infecting 8089 individuals and causing 774 deaths. In 2012, Middle East Respiratory Syndrome-Coronavirus (MERS-CoV) emerged in Saudi Arabia and has spread to 27 countries, with a mortality rate of ~34%. In 2019, SARS-CoV-2 emerged and has spread to 220 countries, infecting over 100,000,000 people and causing more than 2,000,000 deaths to date. These three human coronaviruses cause diseases of varying severity. Most people develop mild, common cold-like symptoms, while some develop acute respiratory distress syndrome (ARDS). The success of all viruses, including coronaviruses, relies on their evolved abilities to evade and modulate the host anti-viral and pro-inflammatory immune responses. However, we still do not fully understand the transmission, phylogeny, epidemiology, and pathogenesis of MERS-CoV and SARS-CoV-1 and -2. Despite the rapid application of a range of therapies for SARS-CoV-2, such as convalescent plasma, remdesivir, hydroxychloroquine and type I interferon, no fully effective treatment has been determined. Remarkably, COVID-19 vaccine research and development have produced several offerings that are now been administered worldwide. Here, we summarise an up-to-date understanding of epidemiology, immunomodulation and ongoing anti-viral and immunosuppressive treatment strategies. Indeed, understanding the interplay between coronaviruses and the anti-viral immune response is crucial to identifying novel targets for therapeutic intervention, which may even prove invaluable for the control of future emerging coronavirus.
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Affiliation(s)
- Yamei Zhang
- Viral Immunology Group, School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, D02 R590 Dublin, Ireland; (Y.Z.); (S.G.)
| | - Siobhan Gargan
- Viral Immunology Group, School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, D02 R590 Dublin, Ireland; (Y.Z.); (S.G.)
| | - Yongxu Lu
- Department of Pathology, University of Cambridge, Cambridge CB2 1QP, UK;
| | - Nigel J. Stevenson
- Viral Immunology Group, School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, D02 R590 Dublin, Ireland; (Y.Z.); (S.G.)
- Viral Immunology Group, Royal College of Surgeons in Ireland—Medical University of Bahrain, Adliya 15503, Bahrain
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Du Y, Xu Y, Feng J, Hu L, Zhang Y, Zhang B, Guo W, Mai R, Chen L, Fang J, Zhang H, Peng T. Intranasal administration of a recombinant RBD vaccine induced protective immunity against SARS-CoV-2 in mouse. Vaccine 2021; 39:2280-2287. [PMID: 33731271 PMCID: PMC7934688 DOI: 10.1016/j.vaccine.2021.03.006] [Citation(s) in RCA: 43] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2020] [Revised: 01/06/2021] [Accepted: 03/02/2021] [Indexed: 12/13/2022]
Abstract
The emergence of the global Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) pandemic underscores the importance of the rapid development of a non-invasive vaccine that can be easily administered. A vaccine administered by nasal delivery is endowed with such characteristics against respiratory viruses. In this study, we generated a recombinant SARS-CoV-2 receptor-binding domain (RBD)-based subunit vaccine. Mice were immunized via intranasal inoculation, microneedle-intradermal injection, or intramuscular injection, after which the RBD-specific immune responses were compared. Results showed that when administrated intranasally, the vaccine elicited a robust systemic humoral immunity with high titers of IgG antibodies and neutralizing antibodies as well as a significant mucosal immunity. Besides, antigen-specific T cell responses were also analyzed. These results indicated that the non-invasive intranasal administration should be explored for the future SARS-CoV-2 vaccine design.
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Affiliation(s)
- Yingying Du
- Institute of Human Virology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, Guangdong, China
| | - Yuhua Xu
- Guangdong South China Vaccine, Guangzhou, China
| | - Jin Feng
- Guangdong South China Vaccine, Guangzhou, China
| | - Longbo Hu
- Sino-French Hoffmann Institute of Immunology, State Key Laboratory of Respiratory Disease, College of Basic Medical Science, Guangzhou Medical University, Guangzhou, China
| | - Yanan Zhang
- Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China
| | - Bo Zhang
- Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China
| | - Weili Guo
- Guangdong South China Vaccine, Guangzhou, China
| | - Runming Mai
- Guangdong South China Vaccine, Guangzhou, China
| | - Liyun Chen
- Guangdong South China Vaccine, Guangzhou, China
| | - Jianmin Fang
- Sino-French Hoffmann Institute of Immunology, State Key Laboratory of Respiratory Disease, College of Basic Medical Science, Guangzhou Medical University, Guangzhou, China
| | - Hui Zhang
- Institute of Human Virology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, Guangdong, China.
| | - Tao Peng
- Guangdong South China Vaccine, Guangzhou, China; Sino-French Hoffmann Institute of Immunology, State Key Laboratory of Respiratory Disease, College of Basic Medical Science, Guangzhou Medical University, Guangzhou, China.
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Chung JY, Thone MN, Kwon YJ. COVID-19 vaccines: The status and perspectives in delivery points of view. Adv Drug Deliv Rev 2021; 170:1-25. [PMID: 33359141 PMCID: PMC7759095 DOI: 10.1016/j.addr.2020.12.011] [Citation(s) in RCA: 234] [Impact Index Per Article: 58.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2020] [Revised: 12/15/2020] [Accepted: 12/17/2020] [Indexed: 12/29/2022]
Abstract
Due to the high prevalence and long incubation periods often without symptoms, the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has infected millions of individuals globally, causing the coronavirus disease 2019 (COVID-19) pandemic. Even with the recent approval of the anti-viral drug, remdesivir, and Emergency Use Authorization of monoclonal antibodies against S protein, bamlanivimab and casirimab/imdevimab, efficient and safe COVID-19 vaccines are still desperately demanded not only to prevent its spread but also to restore social and economic activities via generating mass immunization. Recent Emergency Use Authorization of Pfizer and BioNTech's mRNA vaccine may provide a pathway forward, but monitoring of long-term immunity is still required, and diverse candidates are still under development. As the knowledge of SARS-CoV-2 pathogenesis and interactions with the immune system continues to evolve, a variety of drug candidates are under investigation and in clinical trials. Potential vaccines and therapeutics against COVID-19 include repurposed drugs, monoclonal antibodies, antiviral and antigenic proteins, peptides, and genetically engineered viruses. This paper reviews the virology and immunology of SARS-CoV-2, alternative therapies for COVID-19 to vaccination, principles and design considerations in COVID-19 vaccine development, and the promises and roles of vaccine carriers in addressing the unique immunopathological challenges presented by the disease.
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Affiliation(s)
- Jee Young Chung
- Department of Pharmaceutical Sciences, University of California, Irvine, CA 92697, United States of America
| | - Melissa N Thone
- Department of Pharmaceutical Sciences, University of California, Irvine, CA 92697, United States of America
| | - Young Jik Kwon
- Department of Pharmaceutical Sciences, University of California, Irvine, CA 92697, United States of America; Department of Chemical and Biomolecular Engineering, University of California, Irvine, CA 92697, United States of America; Department of Molecular Biology and Biochemistry, University of California, Irvine, CA 92697, United States of America; Department of Biomedical Engineering, University of California, Irvine, CA 92697, United States of America.
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40
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Molaei S, Dadkhah M, Asghariazar V, Karami C, Safarzadeh E. The immune response and immune evasion characteristics in SARS-CoV, MERS-CoV, and SARS-CoV-2: Vaccine design strategies. Int Immunopharmacol 2021; 92:107051. [PMID: 33429331 PMCID: PMC7522676 DOI: 10.1016/j.intimp.2020.107051] [Citation(s) in RCA: 29] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2020] [Revised: 09/24/2020] [Accepted: 09/24/2020] [Indexed: 01/25/2023]
Abstract
The worldwide outbreak of SARS-CoV-2, severe acute respiratory syndrome coronavirus 2 as a novel human coronavirus, was the worrying news at the beginning of 2020. Since its emergence complicated more than 870,000 individuals and led to more than 43,000 deaths worldwide. Considering to the potential threat of a pandemic and transmission severity of it, there is an urgent need to evaluate and realize this new virus's structure and behavior and the immunopathology of this disease to find potential therapeutic protocols and to design and develop effective vaccines. This disease is able to agitate the response of the immune system in the infected patients, so ARDS, as a common consequence of immunopathological events for infections with Middle East respiratory syndrome coronavirus (MERS-CoV), SARS-CoV, and SARS-CoV-2, could be the main reason for death. Here, we summarized the immune response and immune evasion characteristics in SARS-CoV, MERS-CoV, and SARS-CoV-2 and therapeutic and prophylactic strategies with a focus on vaccine development and its challenges.
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Affiliation(s)
- Soheila Molaei
- Deputy of Research & Technology, Ardabil University of Medical Sciences, Ardabil, Iran; Pharmaceutical Sciences Research Center, Ardabil University of Medical Sciences, Ardabil, Iran
| | - Masoomeh Dadkhah
- Pharmaceutical Sciences Research Center, Ardabil University of Medical Sciences, Ardabil, Iran; Department of Pharmacology, School of Pharmacy, Ardabil University of Medical Sciences, Ardabil, Iran
| | - Vahid Asghariazar
- Deputy of Research & Technology, Ardabil University of Medical Sciences, Ardabil, Iran
| | - Chiman Karami
- Department of Microbiology, Parasitology, and Immunology, Ardabil University of Medical Sciences, Ardabil, Iran
| | - Elham Safarzadeh
- Department of Microbiology, Parasitology, and Immunology, Ardabil University of Medical Sciences, Ardabil, Iran.
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Singh R, Kang A, Luo X, Jeyanathan M, Gillgrass A, Afkhami S, Xing Z. COVID-19: Current knowledge in clinical features, immunological responses, and vaccine development. FASEB J 2021; 35:e21409. [PMID: 33577115 PMCID: PMC7898934 DOI: 10.1096/fj.202002662r] [Citation(s) in RCA: 46] [Impact Index Per Article: 11.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2020] [Revised: 01/12/2021] [Accepted: 01/19/2021] [Indexed: 01/08/2023]
Abstract
The COVID-19 pandemic has unfolded to be the most challenging global health crisis in a century. In 11 months since its first emergence, according to WHO, the causative infectious agent SARS-CoV-2 has infected more than 100 million people and claimed more than 2.15 million lives worldwide. Moreover, the world has raced to understand the virus and natural immunity and to develop vaccines. Thus, within a short 11 months a number of highly promising COVID-19 vaccines were developed at an unprecedented speed and are now being deployed via emergency use authorization for immunization. Although a considerable number of review contributions are being published, all of them attempt to capture only a specific aspect of COVID-19 or its therapeutic approaches based on ever-expanding information. Here, we provide a comprehensive overview to conceptually thread together the latest information on global epidemiology and mitigation strategies, clinical features, viral pathogenesis and immune responses, and the current state of vaccine development.
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Affiliation(s)
- Ramandeep Singh
- McMaster Immunology Research CentreM. G. DeGroote Institute for Infectious Disease Research & Department of MedicineMcMaster UniversityHamiltonONCanada
| | - Alisha Kang
- McMaster Immunology Research CentreM. G. DeGroote Institute for Infectious Disease Research & Department of MedicineMcMaster UniversityHamiltonONCanada
| | - Xiangqian Luo
- McMaster Immunology Research CentreM. G. DeGroote Institute for Infectious Disease Research & Department of MedicineMcMaster UniversityHamiltonONCanada
- Department of Pediatric OtolaryngologyShenzhen HospitalSouthern Medical UniversityShenzhenChina
| | - Mangalakumari Jeyanathan
- McMaster Immunology Research CentreM. G. DeGroote Institute for Infectious Disease Research & Department of MedicineMcMaster UniversityHamiltonONCanada
| | - Amy Gillgrass
- McMaster Immunology Research CentreM. G. DeGroote Institute for Infectious Disease Research & Department of MedicineMcMaster UniversityHamiltonONCanada
| | - Sam Afkhami
- McMaster Immunology Research CentreM. G. DeGroote Institute for Infectious Disease Research & Department of MedicineMcMaster UniversityHamiltonONCanada
| | - Zhou Xing
- McMaster Immunology Research CentreM. G. DeGroote Institute for Infectious Disease Research & Department of MedicineMcMaster UniversityHamiltonONCanada
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Septyaningtrias DE, Susilowati R. Neurological involvement of COVID-19: from neuroinvasion and neuroimmune crosstalk to long-term consequences. Rev Neurosci 2021; 32:427-442. [PMID: 33550780 DOI: 10.1515/revneuro-2020-0092] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2020] [Accepted: 11/07/2020] [Indexed: 12/12/2022]
Abstract
As the coronavirus disease 2019 (COVID-19) pandemic continues to be a multidimensional threat to humanity, more evidence of neurological involvement associated with it has emerged. Neuroimmune interaction may prove to be important not only in the pathogenesis of neurological manifestations but also to prevent systemic hyperinflammation. In this review, we summarize reports of COVID-19 cases with neurological involvement, followed by discussion of possible routes of entry, immune responses against coronavirus infection in the central nervous system and mechanisms of nerve degeneration due to viral infection and immune responses. Possible mechanisms for neuroprotection and virus-associated neurological consequences are also discussed.
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Affiliation(s)
- Dian Eurike Septyaningtrias
- Department of Histology and Cell Biology, Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada, Jalan Farmako Sekip Utara, Yogyakarta55281, Indonesia
| | - Rina Susilowati
- Department of Histology and Cell Biology, Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada, Jalan Farmako Sekip Utara, Yogyakarta55281, Indonesia
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43
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Butler SE, Crowley AR, Natarajan H, Xu S, Weiner JA, Bobak CA, Mattox DE, Lee J, Wieland-Alter W, Connor RI, Wright PF, Ackerman ME. Distinct Features and Functions of Systemic and Mucosal Humoral Immunity Among SARS-CoV-2 Convalescent Individuals. Front Immunol 2021; 11:618685. [PMID: 33584712 PMCID: PMC7876222 DOI: 10.3389/fimmu.2020.618685] [Citation(s) in RCA: 72] [Impact Index Per Article: 18.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2020] [Accepted: 12/21/2020] [Indexed: 12/18/2022] Open
Abstract
Understanding humoral immune responses to SARS-CoV-2 infection will play a critical role in the development of vaccines and antibody-based interventions. We report systemic and mucosal antibody responses in convalescent individuals who experienced varying severity of disease. Whereas assessment of neutralization and antibody-mediated effector functions revealed polyfunctional antibody responses in serum, only robust neutralization and phagocytosis were apparent in nasal wash samples. Serum neutralization and effector functions correlated with systemic SARS-CoV-2-specific IgG response magnitude, while mucosal neutralization was associated with nasal SARS-CoV-2-specific IgA. Antibody depletion experiments support the mechanistic relevance of these correlations. Associations between nasal IgA responses, virus neutralization at the mucosa, and less severe disease suggest the importance of assessing mucosal immunity in larger natural infection cohorts. Further characterization of antibody responses at the portal of entry may define their ability to contribute to protection from infection or reduced risk of hospitalization, informing public health assessment strategies and vaccine development efforts.
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Affiliation(s)
- Savannah E. Butler
- Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Dartmouth College, Hanover, NH, United States
| | - Andrew R. Crowley
- Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Dartmouth College, Hanover, NH, United States
| | - Harini Natarajan
- Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Dartmouth College, Hanover, NH, United States
| | - Shiwei Xu
- Program in Quantitative and Biology Sciences, Dartmouth College, Hanover, NH, United States
| | - Joshua A. Weiner
- Thayer School of Engineering, Dartmouth College, Hanover, NH, United States
| | - Carly A. Bobak
- Program in Quantitative and Biology Sciences, Dartmouth College, Hanover, NH, United States
| | - Daniel E. Mattox
- Department of Computer Science, Dartmouth College, Hanover, NH, United States
| | - Jiwon Lee
- Thayer School of Engineering, Dartmouth College, Hanover, NH, United States
| | - Wendy Wieland-Alter
- Department of Pediatrics, Geisel School of Medicine at Dartmouth, Dartmouth-Hitchcock Medical Center, Lebanon, NH, United States
| | - Ruth I. Connor
- Department of Pediatrics, Geisel School of Medicine at Dartmouth, Dartmouth-Hitchcock Medical Center, Lebanon, NH, United States
| | - Peter F. Wright
- Department of Pediatrics, Geisel School of Medicine at Dartmouth, Dartmouth-Hitchcock Medical Center, Lebanon, NH, United States
| | - Margaret E. Ackerman
- Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Dartmouth College, Hanover, NH, United States
- Program in Quantitative and Biology Sciences, Dartmouth College, Hanover, NH, United States
- Thayer School of Engineering, Dartmouth College, Hanover, NH, United States
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Sterlin D, Mathian A, Miyara M, Mohr A, Anna F, Claër L, Quentric P, Fadlallah J, Devilliers H, Ghillani P, Gunn C, Hockett R, Mudumba S, Guihot A, Luyt CE, Mayaux J, Beurton A, Fourati S, Bruel T, Schwartz O, Lacorte JM, Yssel H, Parizot C, Dorgham K, Charneau P, Amoura Z, Gorochov G. IgA dominates the early neutralizing antibody response to SARS-CoV-2. Sci Transl Med 2021; 13:eabd2223. [PMID: 33288662 PMCID: PMC7857408 DOI: 10.1126/scitranslmed.abd2223] [Citation(s) in RCA: 749] [Impact Index Per Article: 187.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2020] [Revised: 08/26/2020] [Accepted: 12/01/2020] [Indexed: 12/12/2022]
Abstract
Humoral immune responses are typically characterized by primary IgM antibody responses followed by secondary antibody responses associated with immune memory and composed of IgG, IgA, and IgE. Here, we measured acute humoral responses to SARS-CoV-2, including the frequency of antibody-secreting cells and the presence of SARS-CoV-2-specific neutralizing antibodies in the serum, saliva, and bronchoalveolar fluid of 159 patients with COVID-19. Early SARS-CoV-2-specific humoral responses were dominated by IgA antibodies. Peripheral expansion of IgA plasmablasts with mucosal homing potential was detected shortly after the onset of symptoms and peaked during the third week of the disease. The virus-specific antibody responses included IgG, IgM, and IgA, but IgA contributed to virus neutralization to a greater extent compared with IgG. Specific IgA serum concentrations decreased notably 1 month after the onset of symptoms, but neutralizing IgA remained detectable in saliva for a longer time (days 49 to 73 post-symptoms). These results represent a critical observation given the emerging information as to the types of antibodies associated with optimal protection against reinfection and whether vaccine regimens should consider targeting a potent but potentially short-lived IgA response.
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Affiliation(s)
- Delphine Sterlin
- Sorbonne Université, Inserm, Centre d'Immunologie et des Maladies Infectieuses (CIMI-Paris), 91 boulevard de l'Hôpital, 75013 Paris, France
- Département d'Immunologie, Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Pitié-Salpêtrière, 83 boulevard de l'Hôpital, 75013 Paris, France
- Unit of Antibodies in Therapy and Pathology, Institut Pasteur, UMR1222, Inserm, 25-28 Rue du Dr Roux, 75015 Paris, France
| | - Alexis Mathian
- Sorbonne Université, Inserm, Centre d'Immunologie et des Maladies Infectieuses (CIMI-Paris), 91 boulevard de l'Hôpital, 75013 Paris, France
- Service de Médecine Interne 2, Institut E3M, AP-HP, Hôpital Pitié-Salpêtrière, 83 boulevard de l'Hôpital, 75013 Paris, France
| | - Makoto Miyara
- Sorbonne Université, Inserm, Centre d'Immunologie et des Maladies Infectieuses (CIMI-Paris), 91 boulevard de l'Hôpital, 75013 Paris, France
- Département d'Immunologie, Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Pitié-Salpêtrière, 83 boulevard de l'Hôpital, 75013 Paris, France
| | - Audrey Mohr
- Sorbonne Université, Inserm, Centre d'Immunologie et des Maladies Infectieuses (CIMI-Paris), 91 boulevard de l'Hôpital, 75013 Paris, France
| | - François Anna
- Unité de Virologie Moléculaire et Vaccinologie, Institut Pasteur, 25-28 Rue du Dr Roux, 75015 Paris, France
- Theravectys, Institut Pasteur, 25-28 Rue du Dr Roux, 75015 Paris, France
| | - Laetitia Claër
- Sorbonne Université, Inserm, Centre d'Immunologie et des Maladies Infectieuses (CIMI-Paris), 91 boulevard de l'Hôpital, 75013 Paris, France
| | - Paul Quentric
- Sorbonne Université, Inserm, Centre d'Immunologie et des Maladies Infectieuses (CIMI-Paris), 91 boulevard de l'Hôpital, 75013 Paris, France
| | - Jehane Fadlallah
- Sorbonne Université, Inserm, Centre d'Immunologie et des Maladies Infectieuses (CIMI-Paris), 91 boulevard de l'Hôpital, 75013 Paris, France
- Service de Médecine Interne 2, Institut E3M, AP-HP, Hôpital Pitié-Salpêtrière, 83 boulevard de l'Hôpital, 75013 Paris, France
| | - Hervé Devilliers
- Centre Hospitalier Universitaire de Dijon, Hôpital François Mitterrand, service de médecine interne et maladies systémiques (médecine interne 2) et Centre d'Investigation Clinique, Inserm CIC-EC 1432, 3 rue du FBG Raines, 21000 Dijon, France
| | - Pascale Ghillani
- Département d'Immunologie, Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Pitié-Salpêtrière, 83 boulevard de l'Hôpital, 75013 Paris, France
| | - Cary Gunn
- Genalyte Inc., 10520 Wateridge Circle, San Diego, CA 92121, USA
| | - Rick Hockett
- Genalyte Inc., 10520 Wateridge Circle, San Diego, CA 92121, USA
| | - Sasi Mudumba
- Genalyte Inc., 10520 Wateridge Circle, San Diego, CA 92121, USA
| | - Amélie Guihot
- Sorbonne Université, Inserm, Centre d'Immunologie et des Maladies Infectieuses (CIMI-Paris), 91 boulevard de l'Hôpital, 75013 Paris, France
- Département d'Immunologie, Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Pitié-Salpêtrière, 83 boulevard de l'Hôpital, 75013 Paris, France
| | - Charles-Edouard Luyt
- Service de Médecine Intensive Réanimation, Institut de Cardiologie, APHP, Sorbonne-Université, Hôpital Pitié-Salpêtrière, 83 boulevard de l'Hôpital, 75013 Paris, France
- Sorbonne Université, INSERM, UMRS 1166-ICAN Institute of Cardiometabolism and Nutrition, 91 boulevard de l'Hôpital, 75013 Paris, France
| | - Julien Mayaux
- Service de Médecine Intensive-Réanimation et Pneumologie, APHP, Hôpital Pitié-Salpêtrière, 83 boulevard de l'Hôpital, 75013 Paris, France
| | - Alexandra Beurton
- Service de Médecine Intensive-Réanimation et Pneumologie, APHP, Hôpital Pitié-Salpêtrière, 83 boulevard de l'Hôpital, 75013 Paris, France
- Sorbonne Université, Inserm UMRS Neurophysiologie respiratoire expérimentale et clinique, AP-HP, 91 boulevard de l'Hôpital, 75013 Paris, France
| | - Salma Fourati
- Service de Biochimie Endocrinienne et Oncologique, AP-HP, Hôpital Pitié-Salpêtrière, 83 boulevard de l'Hôpital, 75013 Paris, France
- Inserm UMR1149, Centre de Recherche sur l'Inflammation Paris Montmartre (CRI), 16 rue Henri Huchard, 75890 Paris, France
| | - Timothée Bruel
- Virus and Immunity Unit, Department of Virology, Institut Pasteur, 25-28 Rue du Dr Roux, 75015 Paris, France
- CNRS-UMR3569, Institut Pasteur, 25-28 Rue du Dr Roux, 75015 Paris, France
- Vaccine Research Institute, 51 avenue du Maréchal de Lattre de Tassigny, 94000 Créteil, France
| | - Olivier Schwartz
- Virus and Immunity Unit, Department of Virology, Institut Pasteur, 25-28 Rue du Dr Roux, 75015 Paris, France
- CNRS-UMR3569, Institut Pasteur, 25-28 Rue du Dr Roux, 75015 Paris, France
- Vaccine Research Institute, 51 avenue du Maréchal de Lattre de Tassigny, 94000 Créteil, France
| | - Jean-Marc Lacorte
- Sorbonne Université, INSERM, UMRS 1166-ICAN Institute of Cardiometabolism and Nutrition, 91 boulevard de l'Hôpital, 75013 Paris, France
- Service de Biochimie Endocrinienne et Oncologique, AP-HP, Hôpital Pitié-Salpêtrière, 83 boulevard de l'Hôpital, 75013 Paris, France
| | - Hans Yssel
- Sorbonne Université, Inserm, Centre d'Immunologie et des Maladies Infectieuses (CIMI-Paris), 91 boulevard de l'Hôpital, 75013 Paris, France
| | - Christophe Parizot
- Sorbonne Université, Inserm, Centre d'Immunologie et des Maladies Infectieuses (CIMI-Paris), 91 boulevard de l'Hôpital, 75013 Paris, France
- Département d'Immunologie, Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Pitié-Salpêtrière, 83 boulevard de l'Hôpital, 75013 Paris, France
| | - Karim Dorgham
- Sorbonne Université, Inserm, Centre d'Immunologie et des Maladies Infectieuses (CIMI-Paris), 91 boulevard de l'Hôpital, 75013 Paris, France
| | - Pierre Charneau
- Unité de Virologie Moléculaire et Vaccinologie, Institut Pasteur, 25-28 Rue du Dr Roux, 75015 Paris, France
- Theravectys, Institut Pasteur, 25-28 Rue du Dr Roux, 75015 Paris, France
| | - Zahir Amoura
- Sorbonne Université, Inserm, Centre d'Immunologie et des Maladies Infectieuses (CIMI-Paris), 91 boulevard de l'Hôpital, 75013 Paris, France
- Service de Médecine Interne 2, Institut E3M, AP-HP, Hôpital Pitié-Salpêtrière, 83 boulevard de l'Hôpital, 75013 Paris, France
| | - Guy Gorochov
- Sorbonne Université, Inserm, Centre d'Immunologie et des Maladies Infectieuses (CIMI-Paris), 91 boulevard de l'Hôpital, 75013 Paris, France.
- Département d'Immunologie, Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Pitié-Salpêtrière, 83 boulevard de l'Hôpital, 75013 Paris, France
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45
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Zhou D, Tian X, Qi R, Peng C, Zhang W. Identification of 22 N-glycosites on spike glycoprotein of SARS-CoV-2 and accessible surface glycopeptide motifs: Implications for vaccination and antibody therapeutics. Glycobiology 2021; 31:69-80. [PMID: 32518941 PMCID: PMC7313968 DOI: 10.1093/glycob/cwaa052] [Citation(s) in RCA: 36] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2020] [Revised: 05/28/2020] [Accepted: 06/01/2020] [Indexed: 12/17/2022] Open
Abstract
Coronaviruses hijack human enzymes to assemble the sugar coat on their spike glycoproteins. The mechanisms by which human antibodies may recognize the antigenic viral peptide epitopes hidden by the sugar coat are unknown. Glycosylation by insect cells differs from the native form produced in human cells, but insect cell-derived influenza vaccines have been approved by the US Food and Drug Administration. In this study, we analyzed recombinant severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein secreted from BTI-Tn-5B1-4 insect cells, by trypsin and chymotrypsin digestion followed by mass spectrometry analysis. We acquired tandem mass spectrometry (MS/MS) spectrums for glycopeptides of all 22 predicted N-glycosylated sites. We further analyzed the surface accessibility of spike proteins according to cryogenic electron microscopy and homolog-modeled structures and available antibodies that bind to SARS-CoV-1. All 22 N-glycosylated sites of SARS-CoV-2 are modified by high-mannose N-glycans. MS/MS fragmentation clearly established the glycopeptide identities. Electron densities of glycans cover most of the spike receptor-binding domain of SARS-CoV-2, except YQAGSTPCNGVEGFNCYFPLQSYGFQPTNGVGYQ, similar to a region FSPDGKPCTPPALNCYWPLNDYGFYTTTGIGYQ in SARS-CoV-1. Other surface-exposed domains include those located on central helix, connecting region, heptad repeats and N-terminal domain. Because the majority of antibody paratopes bind to the peptide portion with or without sugar modification, we propose a snake-catching model for predicted paratopes: a minimal length of peptide is first clamped by a paratope and sugar modifications close to the peptide either strengthen or do not hinder the binding.
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Affiliation(s)
- Dapeng Zhou
- Tongji University School of Medicine, 1239 Siping Road, Shanghai 200092, China.,Shanghai Pudong New Area Mental Health Center affiliated with Tongji University School of Medicine, 165 Sanlin Road, Shanghai 200124, China
| | - Xiaoxu Tian
- National Facility for Protein Science in Shanghai, Zhangjiang Lab, Shanghai Advanced Research Institute, Chinese Academy of Science, 333 Haike Road, Shanghai 201210, China
| | - Ruibing Qi
- Innovation Team of Small Animal Infectious Disease, Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Science, 518 Ziyue Road, Shanghai 200241, China
| | - Chao Peng
- National Facility for Protein Science in Shanghai, Zhangjiang Lab, Shanghai Advanced Research Institute, Chinese Academy of Science, 333 Haike Road, Shanghai 201210, China
| | - Wen Zhang
- Fudan University Pudong Medical Center, Institutes of Biomedical Sciences, 200433 Gongwei Road, Shanghai, China.,Department of Systems Biology for Medicine, Shanghai Medical College, Fudan University, 138 Yixueyuan Road, Shanghai 200032, China
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Oroojalian F, Haghbin A, Baradaran B, Hemmat N, Shahbazi MA, Baghi HB, Mokhtarzadeh A, Hamblin MR. Novel insights into the treatment of SARS-CoV-2 infection: An overview of current clinical trials. Int J Biol Macromol 2020; 165:18-43. [PMID: 32991900 PMCID: PMC7521454 DOI: 10.1016/j.ijbiomac.2020.09.204] [Citation(s) in RCA: 31] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2020] [Revised: 09/15/2020] [Accepted: 09/22/2020] [Indexed: 12/13/2022]
Abstract
The emergence of the global pandemic caused by the novel SARS-CoV-2 virus has motivated scientists to find a definitive treatment or a vaccine against it in the shortest possible time. Current efforts towards this goal remain fruitless without a full understanding of the behavior of the virus and its adaptor proteins. This review provides an overview of the biological properties, functional mechanisms, and molecular components of SARS-CoV-2, along with investigational therapeutic and preventive approaches for this virus. Since the proteolytic cleavage of the S protein is critical for virus penetration into cells, a set of drugs, such as chloroquine, hydroxychloroquine, camostat mesylate have been tested in clinical trials to suppress this event. In addition to angiotensin-converting enzyme 2, the role of CD147 in the viral entrance has also been proposed. Mepolizumab has shown to be effective in blocking the virus's cellular entrance. Antiviral drugs, such as remdesivir, ritonavir, oseltamivir, darunavir, lopinavir, zanamivir, peramivir, and oseltamivir, have also been tested as treatments for COVID-19. Regarding preventive vaccines, the whole virus, vectors, nucleic acids, and structural subunits have been suggested for vaccine development. Mesenchymal stem cells and natural killer cells could also be used against SARS-CoV-2. All the above-mentioned strategies, as well as the role of nanomedicine for the diagnosis and treatment of SARS-CoV-2 infection, have been discussed in this review.
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Affiliation(s)
- Fatemeh Oroojalian
- Department of Advanced Sciences and Technologies in Medicine, School of Medicine, North Khorasan University of Medical Sciences, Bojnurd, Iran; Natural Products and Medicinal Plants Research Center, North Khorasan University of Medical Sciences, Bojnurd, Iran
| | - Ali Haghbin
- Department of Pediatrics, School of Medicine, North Khorasan University of Medical Sciences, Bojnurd, Iran; Natural Products and Medicinal Plants Research Center, North Khorasan University of Medical Sciences, Bojnurd, Iran
| | - Behzad Baradaran
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Nima Hemmat
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran; Infectious and Tropical Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Mohammad-Ali Shahbazi
- Drug Research Program, Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, Helsinki FI-00014, Finland; Department of Pharmaceutical Nanotechnology, School of Pharmacy, Zanjan University of Medical Sciences, Zanjan, Iran
| | - Hossein Bannazadeh Baghi
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran; Infectious and Tropical Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran; Department of Virology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Ahad Mokhtarzadeh
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
| | - Michael R Hamblin
- Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, MA 02114, USA; Department of Dermatology, Harvard Medical School, Boston, MA 02115, USA; Laser Research Centre, Faculty of Health Science, University of Johannesburg, Doornfontein 2028, South Africa.
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47
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Mudgal R, Nehul S, Tomar S. Prospects for mucosal vaccine: shutting the door on SARS-CoV-2. Hum Vaccin Immunother 2020; 16:2921-2931. [PMID: 32931361 PMCID: PMC7544966 DOI: 10.1080/21645515.2020.1805992] [Citation(s) in RCA: 69] [Impact Index Per Article: 13.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2020] [Revised: 07/19/2020] [Accepted: 08/03/2020] [Indexed: 12/25/2022] Open
Abstract
The sudden emergence of a highly transmissible and pathogenic coronavirus SARS-CoV-2 in December 2019 from China and its rapid global spread has posed an international health emergency. The rapid development of an effective vaccine is imperative to control the spread of SARS-CoV-2. A number of concurrent efforts to find an effective therapeutic agent or vaccine for COVID-19 (coronavirus disease 2019) are being undertaken globally. Oral and nasal mucosal surfaces serve as the primary portal of entry for pathogens like coronaviruses in the human body. As evidenced by studies on similar coronaviruses (SARS-CoV and MERS-CoV), mucosal vaccination can provide a safe and effective means for the induction of long-lasting systemic and mucosal immunity to confer protection against SARS-CoV-2. This article summarizes the approaches to an effective mucosal vaccine formulation which can be a rewarding approach to combat the unprecedented threat posed by this emerging global pandemic.
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Affiliation(s)
- Rajat Mudgal
- Department of Biotechnology, Indian Institute of Technology Roorkee, Roorkee, India
| | - Sanketkumar Nehul
- Department of Biotechnology, Indian Institute of Technology Roorkee, Roorkee, India
| | - Shailly Tomar
- Department of Biotechnology, Indian Institute of Technology Roorkee, Roorkee, India
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Soltani S, Zandi M, Shiri Aghbash P, Rezaei M, Mohammadzadeh N, Afsharifar A, Poortahmasebi V. A review of COVID-19 vaccines and major considerations for diabetic patients. Biotechnol Appl Biochem 2020; 69:30-40. [PMID: 33179788 DOI: 10.1002/bab.2076] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2020] [Accepted: 11/05/2020] [Indexed: 01/08/2023]
Abstract
The necessity and impact of SARS-CoV2 on the world's health have led to developing and producing practical and useful vaccines for this deadly respiratory virus. Since April 2020, a vaccine for the virus has been developed. Given that comorbidities such as diabetes, hypertension, and cardiovascular disease are more prone to viruses and the risk of infection, vaccines should be designed to protect against high-risk respiratory illnesses. Including SARS, MERS, influenza, and the SARS-CoV-2 provide a safe immune response. Here, we review the information and studies that have been done to help develop strategies and perspectives for producing a safe and ideal vaccine to prevent COVID-19 in normal people, especially at high-risk groups such as diabetes patients.
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Affiliation(s)
- Saber Soltani
- Department of Virology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.,Research Center for Clinical Virology, Tehran University of Medical Sciences, Tehran, Iran
| | - Milad Zandi
- Department of Virology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.,Research Center for Clinical Virology, Tehran University of Medical Sciences, Tehran, Iran
| | - Parisa Shiri Aghbash
- Department of Bacteriology and Virology, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Masoud Rezaei
- Department of Plant Protection, Shiraz University, Shiraz, Iran
| | - Nader Mohammadzadeh
- Health Reference Laboratory, Tabriz University of Medical Sciences, Tabriz, Iran
| | | | - Vahdat Poortahmasebi
- Department of Bacteriology and Virology, Tabriz University of Medical Sciences, Tabriz, Iran
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Cimolai N. Applying Immune Instincts and Maternal Intelligence from Comparative Microbiology to COVID-19. ACTA ACUST UNITED AC 2020; 2:2670-2683. [PMID: 33195997 PMCID: PMC7652409 DOI: 10.1007/s42399-020-00634-0] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/04/2020] [Indexed: 01/02/2023]
Abstract
New data specific to COVID-19 are emerging quickly on key issues of immunity and prevention, but past research in coronavirology and for other human pathogens (e.g., Mycoplasma pneumoniae) has been available and of great relevance. Considerable study of endemic human coronaviruses has shown that neutralizing antibody correlates with protection, but effective clinical protection is variable for subsequent virus exposure. Animal coronavirus research has emphasized the importance of local mucosal protection (especially IgA) and systemic responses. Animal model and human post-infection studies for SARS-CoV and MERS-CoV are largely corroborative. Whether for passive therapeutic strategies or vaccination, these findings provide a template for COVID-19. Many approaches to vaccination have emerged, and there may be more than one vaccine that will be applied, but individualized obstacles and concerns for administration, efficacy, and safety are inevitable. Regardless of safeguards or promises that may be understood from laboratory or vertebrate experiments, observations from large-scale human trials will ultimately prove to shape the medical future. Focus on common mucosal immunity can be underrated, and equally or more, focus on lactogenic immunity may be underestimated. In understanding both passive immunity and protection, the body is already primed to educate us with decisions of what constitutes protection and harm. This review provides key insights that drive hypotheses into how the instinct of immunity and the intelligence of the maternal component of the common mucosal immune system has already guided us and may continue to do so effectively into a bright and safe future.
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Affiliation(s)
- Nevio Cimolai
- Faculty of Medicine, The University of British Columbia, Vancouver, BC Canada
- Children’s and Women’s Health Centre of British Columbia, 4480 Oak Street, Vancouver, BC V6H3V4 Canada
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50
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Liang Z, Zhu H, Wang X, Jing B, Li Z, Xia X, Sun H, Yang Y, Zhang W, Shi L, Zeng H, Sun B. Adjuvants for Coronavirus Vaccines. Front Immunol 2020; 11:589833. [PMID: 33240278 PMCID: PMC7677582 DOI: 10.3389/fimmu.2020.589833] [Citation(s) in RCA: 147] [Impact Index Per Article: 29.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2020] [Accepted: 10/14/2020] [Indexed: 12/20/2022] Open
Abstract
Vaccine development utilizing various platforms is one of the strategies that has been proposed to address the coronavirus disease 2019 (COVID-19) pandemic. Adjuvants are critical components of both subunit and certain inactivated vaccines because they induce specific immune responses that are more robust and long-lasting. A review of the history of coronavirus vaccine development demonstrates that only a few adjuvants, including aluminum salts, emulsions, and TLR agonists, have been formulated for the severe acute respiratory syndrome-associated coronavirus (SARS-CoV), Middle East respiratory syndrome-related coronavirus (MERS-CoV), and currently the SARS-CoV-2 vaccines in experimental and pre-clinical studies. However, there is still a lack of evidence regarding the effects of the adjuvants tested in coronavirus vaccines. This paper presents an overview of adjuvants that have been formulated in reported coronavirus vaccine studies, which should assist with the design and selection of adjuvants with optimal efficacy and safety profiles for COVID-19 vaccines.
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Affiliation(s)
- Zhihui Liang
- State Key Laboratory of Fine Chemicals, Dalian University of Technology, Dalian, China
- School of Chemical Engineering, Dalian University of Technology, Dalian, China
| | - Haoru Zhu
- State Key Laboratory of Fine Chemicals, Dalian University of Technology, Dalian, China
- School of Chemical Engineering, Dalian University of Technology, Dalian, China
| | - Xin Wang
- School of Chemical Engineering, Dalian University of Technology, Dalian, China
| | - Bo Jing
- School of Chemical Engineering, Dalian University of Technology, Dalian, China
| | - Zifan Li
- School of Chemical Engineering, Dalian University of Technology, Dalian, China
| | - Xinyu Xia
- State Key Laboratory of Fine Chemicals, Dalian University of Technology, Dalian, China
- School of Chemical Engineering, Dalian University of Technology, Dalian, China
| | - Hongwu Sun
- National Engineering Research Center of Immunological Products, Department of Microbiology and Biochemical Pharmacy, College of Pharmacy and Laboratory Medicine, Third Military Medical University, Chongqing, China
| | - Yun Yang
- National Engineering Research Center of Immunological Products, Department of Microbiology and Biochemical Pharmacy, College of Pharmacy and Laboratory Medicine, Third Military Medical University, Chongqing, China
| | - Weiting Zhang
- NCPC Genetech Biotechnology Co., Ltd., Shijiazhuang, China
| | - Li Shi
- Basic Research Department, Shanghai Zerun Biotechnology Co., Ltd., Shanghai, China
| | - Hao Zeng
- National Engineering Research Center of Immunological Products, Department of Microbiology and Biochemical Pharmacy, College of Pharmacy and Laboratory Medicine, Third Military Medical University, Chongqing, China
| | - Bingbing Sun
- State Key Laboratory of Fine Chemicals, Dalian University of Technology, Dalian, China
- School of Chemical Engineering, Dalian University of Technology, Dalian, China
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