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Cornberg M, Sandmann L, Jaroszewicz J, Kennedy P, Lampertico P, Lemoine M, Lens S, Testoni B, Lai-Hung Wong G, Russo FP. EASL Clinical Practice Guidelines on the management of hepatitis B virus infection. J Hepatol 2025:S0168-8278(25)00174-6. [PMID: 40348683 DOI: 10.1016/j.jhep.2025.03.018] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/20/2025] [Accepted: 03/20/2025] [Indexed: 05/14/2025]
Abstract
The updated EASL Clinical Practice Guidelines on the management of hepatitis B virus (HBV) infection provide comprehensive, evidence-based recommendations for its management. Spanning ten thematic sections, the guidelines address diagnostics, treatment goals, treatment indications, therapeutic options, hepatocellular carcinoma surveillance, management of special populations, HBV reactivation prophylaxis, post-transplant care, HBV prevention strategies, and finally address open questions and future research directions. Chronic HBV remains a global health challenge, with over 250 million individuals affected and significant mortality due to cirrhosis and hepatocellular carcinoma. These guidelines emphasise the importance of early diagnosis, risk stratification based on viral and host factors, and tailored antiviral therapy. Attention is given to simplified algorithms, vaccination, and screening to support global HBV elimination targets. The guidelines also discuss emerging biomarkers and evolving definitions of functional and partial cure. Developed through literature review, expert consensus, and a Delphi process, the guidelines aim to equip healthcare providers across disciplines with practical tools to optimise HBV care and outcomes worldwide.
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Marjani A, Alavian SM, Nassiri Toosi M, Alavian SH, Abazari MF, Khamseh A, Jazayeri SM. Hepatitis B virus infection after immunization: How serious it is? An updated review. Clin Exp Med 2025; 25:113. [PMID: 40210771 PMCID: PMC11985588 DOI: 10.1007/s10238-025-01645-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2025] [Accepted: 03/19/2025] [Indexed: 04/12/2025]
Abstract
Infection with hepatitis B virus (HBV) is one of the significant challenges worldwide. Despite the availability of antiviral drugs against this virus, the most critical strategy to prevent HBV infection is HB vaccination. Basically, despite widespread conventional HB vaccination, due to various reasons, including waning of hepatitis B surface antibody (HBsAb) titer after vaccination, the emergence of vaccine-escape mutants, failure to respond to the vaccine due to viral and host factors, levels of response in high-risk individuals and non-responders to conventional HB vaccination remains a major, unsolved and severe concern. This review focuses on the underlying reasons for conventional hepatitis B vaccination failures. It also suggests solutions to overcome these failures by highlighting significant advances in vaccination, including hepatitis B third-generation vaccines and adjuvanted hepatitis B vaccines as efficient alternatives to second-generation vaccines. Potentially, these new strategies will compensate for the shortcomings caused by second-generation vaccines. Adherence to these denouements has a significant role in preventing the circulation of HBV among individuals and reducing the global burden of HBV-related diseases.
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Affiliation(s)
- Arezoo Marjani
- 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
| | | | - Mohssen Nassiri Toosi
- Liver Transplantation Research Center, Tehran University of Medical Sciences, Tehran, Iran
| | | | - Mohammad Foad Abazari
- Research Center for Clinical Virology, Tehran University of Medical Sciences, Tehran, Iran
- Division of Medical Sciences, Island Medical Program, University of British Columbia, Victoria, BC, Canada
| | - Azam Khamseh
- Research Center for Clinical Virology, Tehran University of Medical Sciences, Tehran, Iran
- Department of Bacteriology and Virology, School of Medicine, Shiraz University of Medical Science, Shiraz, Iran
| | - Seyed Mohammad Jazayeri
- 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.
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Hussain Z, Zhang Y, Qiu L, Gou S, Liu K. Exploring Clec9a in dendritic cell-based tumor immunotherapy for molecular insights and therapeutic potentials. NPJ Vaccines 2025; 10:27. [PMID: 39920156 PMCID: PMC11806010 DOI: 10.1038/s41541-025-01084-2] [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: 07/18/2024] [Accepted: 01/30/2025] [Indexed: 02/09/2025] Open
Abstract
The pivotal role of type 1 conventional dendritic cells (cDC1s) in the field of dendritic cell (DC)-based tumor immunotherapies has been gaining increasing recognition due to their superior antigen cross-presentation abilities and essential role in modulating immune responses. This review specifically highlights the C-type lectin receptor family 9 member A (Clec9a or DNGR-1), which is exclusively expressed on cDC1s and plays a pivotal role in augmenting antigen cross-presentation and cytotoxic T lymphocyte (CTL) responses while simultaneously mitigating off-target effects. These effects include the enhancement of the cDC1s cross-presentation, reducing autoimmune responses and systemic inflammation, as well as preventing the non-specific activation of other immune cells. Consequently, these actions may contribute to reduced toxicity and enhanced treatment efficacy in immunotherapy. The exceptional ability of Clec9a to cross-present dead cell-associated antigens and enhance both humoral and CTL responses makes it an optimal receptor for DC-based strategies aimed at strengthening antitumor immunity. This review provides a comprehensive overview of the molecular characterization, expression, and signaling mechanisms of Clec9a. Furthermore, it discusses the role of Clec9a in the induction and functional activation of Clec9a+ cDC1s, with a particular focus on addressing the challenges related to off-target effects and immune tolerance in the development of tumor vaccines. Additionally, this review explores the potential of Clec9a-targeted approaches to enhance the immunogenicity of tumor vaccines and addresses the utilization of Clec9a as a delivery target for specific agonists (such as STING agonists and αGC) to enhance their therapeutic effects. This novel approach leverages Clec9a's capacity to improve the precision and efficacy of these immunomodulatory molecules in tumor treatment. In summary, this review presents compelling evidence positioning Clec9a as a promising target for DC-based tumor immunotherapy, capable of enhancing the efficacy of vaccines and immune responses while minimizing adverse effects.
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Affiliation(s)
- Zubair Hussain
- Department of Pathophysiology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, Henan, China
- Tianjian Laboratory of Advanced Biomedical Sciences, Academy of Medical Sciences, Zhengzhou University, Zhengzhou, Henan, China
- State Key Laboratory of Metabolic dysregulation & the Prevention and Treatment of Esophageal Cancer, Zhengzhou, Henan, China
- Cancer Chemoprevention International Collaboration Laboratory, Zhengzhou, Henan, China
| | - Yueteng Zhang
- Department of Pathophysiology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, Henan, China
| | - Lu Qiu
- Department of Pathology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Shanshan Gou
- Tianjian Laboratory of Advanced Biomedical Sciences, Academy of Medical Sciences, Zhengzhou University, Zhengzhou, Henan, China.
| | - Kangdong Liu
- Department of Pathophysiology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, Henan, China.
- Tianjian Laboratory of Advanced Biomedical Sciences, Academy of Medical Sciences, Zhengzhou University, Zhengzhou, Henan, China.
- State Key Laboratory of Metabolic dysregulation & the Prevention and Treatment of Esophageal Cancer, Zhengzhou, Henan, China.
- Cancer Chemoprevention International Collaboration Laboratory, Zhengzhou, Henan, China.
- China‒US (Henan) Hormel Cancer Institute, Zhengzhou, Henan, China.
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Singh S, Mishra AK, Yachha M, Singh TP, Katiyar H, Kaul A, Dhiman RK, Bhadauria DS, Goel A. Seroprotection achieved with standard four-dose schedule of hepatitis B vaccine in people with chronic kidney disease: A real-life data. Indian J Gastroenterol 2025; 44:88-94. [PMID: 39298024 DOI: 10.1007/s12664-024-01685-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/19/2024] [Accepted: 08/24/2024] [Indexed: 09/21/2024]
Abstract
BACKGROUND AND OBJECTIVES Hepatitis B virus (HBV) infection is common in people with chronic kidney diseases (CKD). The guidelines recommend four doses, 2.0 mL each, of HBV vaccine, given at zero, one, two and six months in these patients. However, real-life data on the effectiveness of this schedule are limited. We retrospectively reviewed the HBV vaccine response in the CKD population. METHODS The study included adult (≥ 18 years) patients with glomerular filtration rate < 60 mL/min, if they had received four doses (each of 2.0 mL volume) of HBV vaccine and anti-HBs titer was measured at ≥ 1 month of the last dose of vaccine. Participants with hepatitis C or human immunodeficiency virus (HIV) coinfection, organ transplant recipients, active or remote malignancy or use of immunosuppressive medication were excluded. Anti-HBs antibody was measured with two different assays with their limits of detection up to 500 mIU/mL and 1000 mIU/mL. The presence of detectable anti-HBs antibody and anti-HBs titer ≥ 10 mIU/mL defined seroconversion and seroprotection, respectively. RESULTS The study included 208 patients (71.9% males; age 44 [33-55] years; CKD stage II/III/IV/V in 1.4%/7.2%/26.4%/64.9%; 46% on maintenance hemodialysis [MHD]). Overall, seroconversion and seroprotection were achieved in 174 (83.7%) and 161 (77.4%) participants and anti-HBs titer, measured three (2-8) months after the fourth dose, was 124 (12-500) mIU/mL. The median anti-HBs antibody levels at ≤ 6, 7-12, 13-24 and 24 months after the fourth doses were 116, 478, 43 and 70 mIU/mL, respectively. Age, body mass index, stage of CKD, serum albumin and dialysis status were not associated with seroprotection (p < 0.05). CONCLUSION A standard vaccination schedule of four 2.0 mL doses of HBV vaccine in CKD patients induces reasonably good and sustained seroprotection.
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Affiliation(s)
- Surender Singh
- Department of Hepatology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, 226 014, India
| | - Ajay Kumar Mishra
- Department of Hepatology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, 226 014, India
| | - Monika Yachha
- Department of Nephrology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, 226 014, India
| | - Thakur Prashant Singh
- Department of Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, 226 014, India
| | - Harshita Katiyar
- Department of Hepatology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, 226 014, India
| | - Anupma Kaul
- Department of Nephrology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, 226 014, India
| | - Radha Krishna Dhiman
- Department of Hepatology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, 226 014, India
| | - Dharmendra Singh Bhadauria
- Department of Nephrology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, 226 014, India
| | - Amit Goel
- Department of Hepatology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, 226 014, India.
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Nahm WJ, Liang SE, Ho RS. The immunogenicity of hepatitis B vaccine in psoriasis patients and by treatment type: A retrospective cohort study. J Eur Acad Dermatol Venereol 2025; 39:e131-e134. [PMID: 38853625 DOI: 10.1111/jdv.20135] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2024] [Accepted: 05/08/2024] [Indexed: 06/11/2024]
Affiliation(s)
- William J Nahm
- New York University Grossman School of Medicine, New York, New York, USA
| | - Sydney E Liang
- The Ronald O. Perelman Department of Dermatology, New York University Grossman School of Medicine, New York, New York, USA
| | - Roger S Ho
- The Ronald O. Perelman Department of Dermatology, New York University Grossman School of Medicine, New York, New York, USA
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Hung I, Lok AS. Overcoming Hepatitis B Vaccine Nonresponsiveness. JAMA 2025; 333:291-292. [PMID: 39616602 DOI: 10.1001/jama.2024.24028] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/29/2025]
Affiliation(s)
- Ivan Hung
- Division of Infectious Diseases, University of Hong Kong, Hong Kong
| | - Anna S Lok
- Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor
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Khudainazarova NS, Granovskiy DL, Kondakova OA, Ryabchevskaya EM, Kovalenko AO, Evtushenko EA, Arkhipenko MV, Nikitin NA, Karpova OV. Prokaryote- and Eukaryote-Based Expression Systems: Advances in Post-Pandemic Viral Antigen Production for Vaccines. Int J Mol Sci 2024; 25:11979. [PMID: 39596049 PMCID: PMC11594041 DOI: 10.3390/ijms252211979] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2024] [Revised: 11/01/2024] [Accepted: 11/02/2024] [Indexed: 11/28/2024] Open
Abstract
This review addresses the ongoing global challenge posed by emerging and evolving viral diseases, underscoring the need for innovative vaccine development strategies. It focuses on the modern approaches to creating vaccines based on recombinant proteins produced in different expression systems, including bacteria, yeast, plants, insects, and mammals. This review analyses the advantages, limitations, and applications of these expression systems for producing vaccine antigens, as well as strategies for designing safer, more effective, and potentially 'universal' antigens. The review discusses the development of vaccines for a range of viral diseases, excluding SARS-CoV-2, which has already been extensively studied. The authors present these findings with the aim of contributing to ongoing research and advancing the development of antiviral vaccines.
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Affiliation(s)
| | | | | | | | | | | | | | - Nikolai A. Nikitin
- Department of Virology, Faculty of Biology, Lomonosov Moscow State University, 119991 Moscow, Russia; (N.S.K.); (D.L.G.); (O.A.K.); (E.M.R.); (A.O.K.); (E.A.E.); (M.V.A.); (O.V.K.)
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Delghandi S, Raoufinia R, Shahtahmasbi S, Meshkat Z, Gouklani H, Gholoobi A. An overview of occult hepatitis B infection (OBI) with emphasis on HBV vaccination. Heliyon 2024; 10:e37097. [PMID: 39281486 PMCID: PMC11402251 DOI: 10.1016/j.heliyon.2024.e37097] [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: 06/12/2024] [Revised: 08/25/2024] [Accepted: 08/27/2024] [Indexed: 09/18/2024] Open
Abstract
Background The prevalence of chronic hepatitis B virus (HBV) poses a significant threat to the lives of 257 million individuals globally, potentially resulting in severe outcomes such as liver cirrhosis or hepatocellular carcinoma. Among the existing preventive measures, yeast-derived vaccines have proven to be the most efficacious approach in combatting hepatitis B. Nonetheless, as scientific inquiries focus more on occult HBV infection (OBI) in vaccinated persons and the lingering risk of vertical transmission affecting 10-30 % of babies born to HBsAg-positive mothers, there is a growing apprehension regarding the inability of HBV vaccines to ensure complete immunity. This study aims to offer a more comprehensive understanding of the implications of widespread HBV vaccination initiatives on OBI while tackling the primary limitations associated with current vaccine formulations. Methods The exploration was conducted on PubMed, Scopus, and Web of Science databases to pinpoint research on OBI within vaccinated cohorts. A sum of 76 suitable studies was recognized. Discussion Multiple studies have documented the occurrence of OBI in fully vaccinated individuals, including both the general population and high-risk groups, such as newborns born to HBsAg-positive mothers. Factors contributing to vaccine failures include low-level anti-HBs antibodies, high maternal viral loads in mother-to-child transmission cases, as well as the presence of vaccine escape mutants and heterologous HBV genotypes. However, further research is needed to precisely understand the impact of active immunization on the emergence of OBI in vaccinated populations. Nonetheless, it is apparent that the advancement of more effective HBV vaccines could potentially lead to the extinction of HBV.
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Affiliation(s)
- Sara Delghandi
- Medical Genetics Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
- Division of Immunology and Genomic Medicine, Center for Cancer Immunotherapy and Immunobiology, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Ramin Raoufinia
- Noncommunicable Diseases Research Center, Neyshabur University of Medical Sciences, Neyshabur, Iran
- Medical Genetics Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Sahar Shahtahmasbi
- Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Zahra Meshkat
- Antimicrobial Resistance Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Hamed Gouklani
- Infectious and Tropical Diseases Research Center, Hormozgan Health Institute, Hormozgan University of Medical Sciences, Bandar Abbas, Iran
| | - Aida Gholoobi
- Medical Genetics Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
- Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
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9
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Garofoli GK. Updated vaccination and screening recommendations for hepatitis B: Implications for pharmacists. J Am Pharm Assoc (2003) 2024; 64:102150. [PMID: 38945211 DOI: 10.1016/j.japh.2024.102150] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2024] [Revised: 05/31/2024] [Accepted: 06/25/2024] [Indexed: 07/02/2024]
Abstract
The number of new infections of hepatitis B is rising and a large number of cases are undiagnosed. These factors are contributing to hepatitis B-related liver complications, including liver cancer, and deaths that could be prevented. The Advisory Committee on Immunization Practices and the Centers for Disease Control and Prevention recently updated vaccination and screening/testing recommendations for hepatitis B. The updated recommendations remove the need for risk assessment before screening or vaccination. Pharmacists will play a key role in a concerted national effort to implement these updated recommendations. A multistakeholder advisory council convened by the Hepatitis B Foundation identified key barriers to screening and vaccination. The council also formulated strategies to optimize implementation of the updated recommendations. These strategies include educating pharmacists about the new recommendations and how they will help to reduce the burden of hepatitis B and liver cancer. Pharmacists could explore establishing pharmacy-provider collaborative practice agreements and potentially leverage capacity built with COVID-19 vaccine implementation. Hospital systems and other clinic settings could update their electronic health records to include prompts for hepatitis B vaccination and screening. Pharmacy systems can implement different reminder options to help patients complete the hepatitis B vaccine series. To address a lack of vaccine confidence, pharmacists can emphasize the cancer prevention benefit of hepatitis B screening and vaccination and engage with patients on an individual level to understand their concerns, assess vaccine status, and discuss vaccine recommendations. Effective implementation of the new recommendations will help achieve national and global goals of eliminating hepatitis B as a public health threat by 2030.
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Hodel KVS, Fiuza BSD, Conceição RS, Aleluia ACM, Pitanga TN, Fonseca LMDS, Valente CO, Minafra-Rezende CS, Machado BAS. Pharmacovigilance in Vaccines: Importance, Main Aspects, Perspectives, and Challenges-A Narrative Review. Pharmaceuticals (Basel) 2024; 17:807. [PMID: 38931474 PMCID: PMC11206969 DOI: 10.3390/ph17060807] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2024] [Revised: 05/29/2024] [Accepted: 06/11/2024] [Indexed: 06/28/2024] Open
Abstract
Pharmacovigilance plays a central role in safeguarding public health by continuously monitoring the safety of vaccines, being critical in a climate of vaccine hesitancy, where public trust is paramount. Pharmacovigilance strategies employed to gather information on adverse events following immunization (AEFIs) include pre-registration data, media reports, clinical trials, and societal reporting. Early detection of AEFIs during clinical trials is crucial for thorough safety analysis and preventing serious reactions once vaccines are deployed. This review highlights the importance of societal reporting, encompassing contributions from community members, healthcare workers, and pharmaceutical companies. Technological advancements such as quick response (QR) codes can facilitate prompt AEFI reporting. While vaccines are demonstrably safe, the possibility of adverse events necessitates continuous post-marketing surveillance. However, underreporting remains a challenge, underscoring the critical role of public engagement in pharmacovigilance. This narrative review comprehensively examines and synthesizes key aspects of virus vaccine pharmacovigilance, with special considerations for specific population groups. We explore applicable legislation, the spectrum of AEFIs associated with major vaccines, and the unique challenges and perspectives surrounding pharmacovigilance in this domain.
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Affiliation(s)
- Katharine Valéria Saraiva Hodel
- SENAI Institute of Innovation (ISI) in Health Advanced Systems (CIMATEC ISI SAS), SENAI CIMATEC University Center, Salvador 41650-010, Bahia State, Brazil
| | - Bianca Sampaio Dotto Fiuza
- SENAI Institute of Innovation (ISI) in Health Advanced Systems (CIMATEC ISI SAS), SENAI CIMATEC University Center, Salvador 41650-010, Bahia State, Brazil
| | - Rodrigo Souza Conceição
- Department of Medicine, College of Pharmacy, Federal University of Bahia, Salvador 40170-115, Bahia State, Brazil
| | - Augusto Cezar Magalhães Aleluia
- SENAI Institute of Innovation (ISI) in Health Advanced Systems (CIMATEC ISI SAS), SENAI CIMATEC University Center, Salvador 41650-010, Bahia State, Brazil
- Department of Natural Sciences, Southwestern Bahia State University (UESB), Campus Vitória da Conquista, Vitória da Conquista 45031-300, Bahia State, Brazil
| | - Thassila Nogueira Pitanga
- SENAI Institute of Innovation (ISI) in Health Advanced Systems (CIMATEC ISI SAS), SENAI CIMATEC University Center, Salvador 41650-010, Bahia State, Brazil
- Laboratory for Research in Genetics and Translational Hematology, Gonçalo Moniz Institute, FIOCRUZ-BA, Salvador 40296-710, Bahia State, Brazil
| | - Larissa Moraes dos Santos Fonseca
- SENAI Institute of Innovation (ISI) in Health Advanced Systems (CIMATEC ISI SAS), SENAI CIMATEC University Center, Salvador 41650-010, Bahia State, Brazil
| | - Camila Oliveira Valente
- SENAI Institute of Innovation (ISI) in Health Advanced Systems (CIMATEC ISI SAS), SENAI CIMATEC University Center, Salvador 41650-010, Bahia State, Brazil
| | | | - Bruna Aparecida Souza Machado
- SENAI Institute of Innovation (ISI) in Health Advanced Systems (CIMATEC ISI SAS), SENAI CIMATEC University Center, Salvador 41650-010, Bahia State, Brazil
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Brinkkemper M, Poniman M, Siteur-van Rijnstra E, Iddouch WA, Bijl TP, Guerra D, Tejjani K, Grobben M, Bhoelan F, Bemelman D, Kempers R, van Gils MJ, Sliepen K, Stegmann T, van der Velden YU, Sanders RW. A spike virosome vaccine induces pan-sarbecovirus antibody responses in mice. iScience 2024; 27:109719. [PMID: 38706848 PMCID: PMC11068555 DOI: 10.1016/j.isci.2024.109719] [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: 11/22/2023] [Revised: 03/08/2024] [Accepted: 04/08/2024] [Indexed: 05/07/2024] Open
Abstract
Zoonotic events by sarbecoviruses have sparked an epidemic (severe acute respiratory syndrome coronavirus [SARS-CoV]) and a pandemic (SARS-CoV-2) in the past two decades. The continued risk of spillovers from animals to humans is an ongoing threat to global health and a pan-sarbecovirus vaccine would be an important contribution to pandemic preparedness. Here, we describe multivalent virosome-based vaccines that present stabilized spike proteins from four sarbecovirus strains, one from each clade. A cocktail of four monovalent virosomes or a mosaic virosome preparation induced broad sarbecovirus binding and neutralizing antibody responses in mice. Pre-existing immunity against SARS-CoV-2 and extending the intervals between immunizations enhanced antibody responses. These results should inform the development of a pan-sarbecovirus vaccine, as part of our efforts to prepare for and/or avoid a next pandemic.
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Affiliation(s)
- Mitch Brinkkemper
- Amsterdam UMC, location University of Amsterdam, Department of Medical Microbiology and Infection Prevention, Meibergdreef 9, 1105 AZ Amsterdam, the Netherlands
- Amsterdam institute for Infection and Immunity, Infectious diseases, Meibergdreef 9, 1105 AZ Amsterdam, the Netherlands
| | - Meliawati Poniman
- Amsterdam UMC, location University of Amsterdam, Department of Medical Microbiology and Infection Prevention, Meibergdreef 9, 1105 AZ Amsterdam, the Netherlands
- Amsterdam institute for Infection and Immunity, Infectious diseases, Meibergdreef 9, 1105 AZ Amsterdam, the Netherlands
| | - Esther Siteur-van Rijnstra
- Amsterdam UMC, location University of Amsterdam, Department of Experimental Immunology, Meibergdreef 9, 1105 AZ Amsterdam, the Netherlands
| | - Widad Ait Iddouch
- Amsterdam UMC, location University of Amsterdam, Department of Medical Microbiology and Infection Prevention, Meibergdreef 9, 1105 AZ Amsterdam, the Netherlands
- Amsterdam institute for Infection and Immunity, Infectious diseases, Meibergdreef 9, 1105 AZ Amsterdam, the Netherlands
| | - Tom P.L. Bijl
- Amsterdam UMC, location University of Amsterdam, Department of Medical Microbiology and Infection Prevention, Meibergdreef 9, 1105 AZ Amsterdam, the Netherlands
- Amsterdam institute for Infection and Immunity, Infectious diseases, Meibergdreef 9, 1105 AZ Amsterdam, the Netherlands
| | - Denise Guerra
- Amsterdam UMC, location University of Amsterdam, Department of Medical Microbiology and Infection Prevention, Meibergdreef 9, 1105 AZ Amsterdam, the Netherlands
- Amsterdam institute for Infection and Immunity, Infectious diseases, Meibergdreef 9, 1105 AZ Amsterdam, the Netherlands
| | - Khadija Tejjani
- Amsterdam UMC, location University of Amsterdam, Department of Medical Microbiology and Infection Prevention, Meibergdreef 9, 1105 AZ Amsterdam, the Netherlands
- Amsterdam institute for Infection and Immunity, Infectious diseases, Meibergdreef 9, 1105 AZ Amsterdam, the Netherlands
| | - Marloes Grobben
- Amsterdam UMC, location University of Amsterdam, Department of Medical Microbiology and Infection Prevention, Meibergdreef 9, 1105 AZ Amsterdam, the Netherlands
- Amsterdam institute for Infection and Immunity, Infectious diseases, Meibergdreef 9, 1105 AZ Amsterdam, the Netherlands
| | - Farien Bhoelan
- Mymetics BV, JH Oortweg 21, CH 2333 Leiden, the Netherlands
| | | | - Ronald Kempers
- Mymetics BV, JH Oortweg 21, CH 2333 Leiden, the Netherlands
| | - Marit J. van Gils
- Amsterdam UMC, location University of Amsterdam, Department of Medical Microbiology and Infection Prevention, Meibergdreef 9, 1105 AZ Amsterdam, the Netherlands
- Amsterdam institute for Infection and Immunity, Infectious diseases, Meibergdreef 9, 1105 AZ Amsterdam, the Netherlands
| | - Kwinten Sliepen
- Amsterdam UMC, location University of Amsterdam, Department of Medical Microbiology and Infection Prevention, Meibergdreef 9, 1105 AZ Amsterdam, the Netherlands
- Amsterdam institute for Infection and Immunity, Infectious diseases, Meibergdreef 9, 1105 AZ Amsterdam, the Netherlands
| | - Toon Stegmann
- Mymetics BV, JH Oortweg 21, CH 2333 Leiden, the Netherlands
| | - Yme U. van der Velden
- Amsterdam UMC, location University of Amsterdam, Department of Medical Microbiology and Infection Prevention, Meibergdreef 9, 1105 AZ Amsterdam, the Netherlands
- Amsterdam institute for Infection and Immunity, Infectious diseases, Meibergdreef 9, 1105 AZ Amsterdam, the Netherlands
| | - Rogier W. Sanders
- Amsterdam UMC, location University of Amsterdam, Department of Medical Microbiology and Infection Prevention, Meibergdreef 9, 1105 AZ Amsterdam, the Netherlands
- Amsterdam institute for Infection and Immunity, Infectious diseases, Meibergdreef 9, 1105 AZ Amsterdam, the Netherlands
- Department of Microbiology and Immunology, Weill Medical College of Cornell University, New York, NY, USA
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Mironova M, Ghany MG. Hepatitis B Vaccine: Four Decades on. Vaccines (Basel) 2024; 12:439. [PMID: 38675820 PMCID: PMC11053833 DOI: 10.3390/vaccines12040439] [Citation(s) in RCA: 6] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2024] [Revised: 04/09/2024] [Accepted: 04/11/2024] [Indexed: 04/28/2024] Open
Abstract
Hepatitis B virus is a substantial contributor to cirrhosis and hepatocellular carcinoma (HCC) globally. Vaccination is the most effective method for prevention of hepatitis B and its associated morbidity and mortality, and the only method to prevent infection with hepatitis D virus. The hepatitis B vaccine has been used worldwide for more than four decades; it is available in a single- or triple-antigen form and in combination with vaccines against other infections. Introduction of the vaccine and administration at birth led to sustained decline in mother-to-child transmission, chronic hepatitis B, and HCC, however, global birth dose coverage remains suboptimal. In this review we will discuss different hepatitis B vaccine formulations and schedules, vaccination guidelines, durability of the response, and vaccine escape mutants, as well as the clinical and economic benefits of vaccination.
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Affiliation(s)
| | - Marc G. Ghany
- Clinical Hepatology Research Section, Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892-1800, USA;
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13
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Demirden SF, Kimiz-Gebologlu I, Oncel SS. Animal Cell Lines as Expression Platforms in Viral Vaccine Production: A Post Covid-19 Perspective. ACS OMEGA 2024; 9:16904-16926. [PMID: 38645343 PMCID: PMC11025085 DOI: 10.1021/acsomega.3c10484] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 12/29/2023] [Revised: 03/11/2024] [Accepted: 03/20/2024] [Indexed: 04/23/2024]
Abstract
Vaccines are considered the most effective tools for preventing diseases. In this sense, with the Covid-19 pandemic, the effects of which continue all over the world, humanity has once again remembered the importance of the vaccine. Also, with the various epidemic outbreaks that occurred previously, the development processes of effective vaccines against these viral pathogens have accelerated. By these efforts, many different new vaccine platforms have been approved for commercial use and have been introduced to the commercial landscape. In addition, innovations have been made in the production processes carried out with conventionally produced vaccine types to create a rapid response to prevent potential epidemics or pandemics. In this situation, various cell lines are being positioned at the center of the production processes of these new generation viral vaccines as expression platforms. Therefore, since the main goal is to produce a fast, safe, and effective vaccine to prevent the disease, in addition to existing expression systems, different cell lines that have not been used in vaccine production until now have been included in commercial production for the first time. In this review, first current viral vaccine types in clinical use today are described. Then, the reason for using cell lines, which are the expression platforms used in the production of these viral vaccines, and the general production processes of cell culture-based viral vaccines are mentioned. Also, selection parameters for animal cell lines as expression platforms in vaccine production are explained by considering bioprocess efficiency and current regulations. Finally, all different cell lines used in cell culture-based viral vaccine production and their properties are summarized, with an emphasis on the current and future status of cell cultures in industrial viral vaccine production.
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Affiliation(s)
| | | | - Suphi S. Oncel
- Ege University, Bioengineering Department, Izmir, 35100, Turkiye
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14
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Sanchez-Martinez ZV, Alpuche-Lazcano SP, Stuible M, Durocher Y. CHO cells for virus-like particle and subunit vaccine manufacturing. Vaccine 2024; 42:2530-2542. [PMID: 38503664 DOI: 10.1016/j.vaccine.2024.03.034] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2024] [Revised: 02/27/2024] [Accepted: 03/13/2024] [Indexed: 03/21/2024]
Abstract
Chinese Hamster Ovary (CHO) cells, employed primarily for manufacturing monoclonal antibodies and other recombinant protein (r-protein) therapeutics, are emerging as a promising host for vaccine antigen production. This is exemplified by the recently approved CHO cell-derived subunit vaccines (SUV) against respiratory syncytial virus (RSV) and varicella-zoster virus (VZV), as well as the enveloped virus-like particle (eVLP) vaccine against hepatitis B virus (HBV). Here, we summarize the design, production, and immunogenicity features of these vaccine and review the most recent progress of other CHO-derived vaccines in pre-clinical and clinical development. We also discuss the challenges associated with vaccine production in CHO cells, with a focus on ensuring viral clearance for eVLP products.
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Affiliation(s)
- Zalma V Sanchez-Martinez
- Human Health Therapeutics Research Centre, National Research Council of Canada, Montreal, QC H4P 2R2, Canada; Department of Biochemistry and Molecular Medicine, University of Montreal, Montreal, QC H3T 1J4, Canada
| | - Sergio P Alpuche-Lazcano
- Human Health Therapeutics Research Centre, National Research Council of Canada, Montreal, QC H4P 2R2, Canada
| | - Matthew Stuible
- Human Health Therapeutics Research Centre, National Research Council of Canada, Montreal, QC H4P 2R2, Canada
| | - Yves Durocher
- Human Health Therapeutics Research Centre, National Research Council of Canada, Montreal, QC H4P 2R2, Canada; Department of Biochemistry and Molecular Medicine, University of Montreal, Montreal, QC H3T 1J4, Canada; PROTEO: The Quebec Network for Research on Protein Function, Structure, and Engineering, Université du Québec à Montréal, 201 Avenue du Président Kennedy, Montréal, QC H2X 3Y7, Canada.
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15
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Yin Z, Wen T, Fu C, Li J, Fang Q, Gong X, You J, Wang S, Zheng C. Comparison of the effectiveness four years after Homo/Hetero prime-boost with 10 μg HP and 20 μg CHO recombinant hepatitis B vaccine at 1 and 6 months in maternal HBsAg-negative children. Front Immunol 2024; 15:1308238. [PMID: 38660313 PMCID: PMC11039823 DOI: 10.3389/fimmu.2024.1308238] [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] [Received: 10/23/2023] [Accepted: 03/29/2024] [Indexed: 04/26/2024] Open
Abstract
Introduction Limited data were available on the effectivenessfour years after Homo or Hetero prime-boost with 10 μg Hansenulapolymorpha recombinant hepatitis B vaccine (HepB-HP) and 20 μgChinese hamster ovary cell HepB (HepB-CHO). Methods A crosssectional study was performed in maternalhepatitis B surface antigen (HBsAg)-negative children whoreceived one dose of 10 μg HepB-HP at birth, Homo or Heteroprime-boost with 10 μg HepB-HP and 20 μg HepB-CHO at 1 and 6months. HBsAg and hepatitis B surface antibody (anti-HBs) fouryears after immunization were quantitatively detected by achemiluminescent microparticle immunoassay (CMIA). Results A total of 359 children were included; 119 childrenreceived two doses of 10 μg HepB-HP and 120 children receivedtwo doses of 20 μg HepB-CHO, called Homo prime-boost; 120children received Hetero prime-boost with 10 μg HepB-HP and 20μg HepB-CHO. All children were HBsAg negative. The geometricmean concentration (GMC) and overall seropositivity rate (SPR) ofanti-HBs were 59.47 (95%CI: 49.00 - 72.16) mIU/ml and 85.51%(307/359). Nearly 15% of the study subjects had an anti-HBsconcentration < 10 mIU/ml and 5.01% had an anti-HBsconcentration ≤ 2.5 mIU/ml. The GMC of the 20 μg CHO Homoprime-boost group [76.05 (95%CI: 54.97 - 105.19) mIU/ml] washigher than that of the 10 μg HP Homo group [45.86 (95%CI:31.94 - 65.84) mIU/ml] (p = 0.035). The GMCs of the Heteroprime-boost groups (10 μg HP-20 μg CHO and 20 μg CHO-10 μgHP) were 75.86 (95% CI: 48.98 - 107.15) mIU/ml and 43.65(95%CI: 27.54 - 69.18) mIU/ml, respectively (p = 0.041). Aftercontrolling for sex influence, the SPR of the 20 μg CHO Homoprime-boost group was 2.087 times than that of the 10 μg HPHomo group. Discussion The HepB booster was not necessary in the generalchildren, Homo/Hetero prime-boost with 20 μg HepB-CHO wouldincrease the anti-HBs concentration four years after immunization,timely testing and improved knowledge about the self-pay vaccinewould be good for controlling hepatitis B.
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Affiliation(s)
- Zhiying Yin
- Department of Immunoprevention, Quzhou Center for Disease Control and Prevention, Quzhou, Zhejiang, China
- School of Public Health, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China
| | - Tingcui Wen
- School of Public Health, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China
| | - Canya Fu
- School of Public Health, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China
| | - Junji Li
- Department of Immunoprevention, Quzhou Center for Disease Control and Prevention, Quzhou, Zhejiang, China
| | - Quanjun Fang
- Department of Immunoprevention, Quzhou Center for Disease Control and Prevention, Quzhou, Zhejiang, China
| | - Xiaoying Gong
- Department of Immunoprevention, Quzhou Center for Disease Control and Prevention, Quzhou, Zhejiang, China
| | - Jialing You
- Department of Microbiology, Quzhou Center for Disease Control and Prevention, Quzhou, Zhejiang, China
| | - Shuangqing Wang
- Department of Immunoprevention, Quzhou Center for Disease Control and Prevention, Quzhou, Zhejiang, China
| | - Canjie Zheng
- Department of Immunoprevention, Quzhou Center for Disease Control and Prevention, Quzhou, Zhejiang, China
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16
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Roggendorf H, Shouval D, Roggendorf M, Gerken G. Longterm Outcome of Therapeutic Vaccination with a Third Generation Pre-S/S HBV Vaccine (PreHevbrio R) of Chronically HBV Infected Patients. J Pers Med 2024; 14:364. [PMID: 38672991 PMCID: PMC11050803 DOI: 10.3390/jpm14040364] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2024] [Revised: 03/13/2024] [Accepted: 03/28/2024] [Indexed: 04/28/2024] Open
Abstract
Several antiviral treatment regimens for chronic hepatitis B (CHB) virus infection have been shown to be effective in suppressing viral load and reducing the risk of hepatocellular injury and its complications. It has been hypothesized that high levels of circulating HBV surface antigen(s) may lead to immune tolerance against HBV and contribute to chronic carriership. Conversely, low-level HBsAg may create a window for the reconstitution of an HBV-specific immune response through vaccination and control of infection. Previous studies in non-responders to yeast-derived HBV vaccines, using a third-generation pre-S/S vaccine, have led to up to 95% anti-HBs seroconversion. This report evaluates the long-term outcome after experimental vaccination with a pre-S/S HBV vaccine intended as a therapeutic intervention in chronic HBV carriers. Four low-level HBsAg carriers (<500 IU/mL) were vaccinated three to seven times with 20 μg PreHevbrioR. Three out of four carriers eliminated HBsAg completely and seroconverted to anti-HBs. One patient seroconverted to anti-HBs but remained with a borderline HBsAg titer (10 IU/mL). Serum anti-HBs levels following repeated vaccination varied between 27 and >1000 IU/L, respectively. Long-term observation (>6 years) showed that after discontinuing NUC treatment for at least two years, HBsAg and HBV DNA remained negative with anti-HBs positive titers ranging between 80 and >1000 IU/L. Based on our preliminary observations, there is a rationale to further evaluate the role of this vaccine as a therapeutic agent.
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Affiliation(s)
- Hedwig Roggendorf
- Institute of Molecular Immunology, University Hospital TUM, 81675 Munich, Germany
| | - Daniel Shouval
- Liver Unit, Hadassah Medical Center, POB 12000, Jerusalem 91120, Israel;
| | - Michael Roggendorf
- Institute of Virology, Technical University of Munich/Helmholtz Zentrum, 81675 Munich, Germany;
| | - Guido Gerken
- Department of Gastroenterology, Helios Klinikum Niedernberg, 42551 Velbert, Germany;
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17
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Al-Busafi SA, Alwassief A. Global Perspectives on the Hepatitis B Vaccination: Challenges, Achievements, and the Road to Elimination by 2030. Vaccines (Basel) 2024; 12:288. [PMID: 38543922 PMCID: PMC10975970 DOI: 10.3390/vaccines12030288] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2024] [Revised: 02/23/2024] [Accepted: 02/27/2024] [Indexed: 10/21/2024] Open
Abstract
Annually, more than 1.5 million preventable new hepatitis B (HBV) infections continue to occur, with an estimated global burden of 296 million individuals living with chronic hepatitis B infection. This substantial health challenge results in over 820,000 annual deaths being attributed to complications such as liver cirrhosis and hepatocellular carcinoma (HCC). The HBV vaccination remains the cornerstone of public health policy to prevent chronic hepatitis B and its related complications. It serves as a crucial element in the global effort to eliminate HBV, as established by the World Health Organization (WHO), with an ambitious 90% vaccination target by 2030. However, reports on global birth dose coverage reveal substantial variability, with an overall coverage rate of only 46%. This comprehensive review thoroughly examines global trends in HBV vaccination coverage, investigating the profound impact of vaccination on HBV prevalence and its consequences across diverse populations, including both high-risk and general demographics. Additionally, the review addresses the essential formidable challenges and facilitating factors for achieving WHO's HBV vaccination coverage objectives and elimination strategies in the coming decade and beyond.
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Affiliation(s)
- Said A. Al-Busafi
- Division of Gastroenterology and Hepatology, Department of Medicine, College of Medicine and Health Sciences, Sultan Qaboos University, Muscat 123, Oman
| | - Ahmed Alwassief
- Division of Gastroenterology and Hepatology, Department of Medicine, Sultan Qaboos University Hospital, Muscat 123, Oman
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18
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Pounraj S, Chen S, Ma L, Mazzieri R, Dolcetti R, Rehm BHA. Targeting Tumor Heterogeneity with Neoantigen-Based Cancer Vaccines. Cancer Res 2024; 84:353-363. [PMID: 38055891 DOI: 10.1158/0008-5472.can-23-2042] [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: 07/10/2023] [Revised: 10/24/2023] [Accepted: 12/04/2023] [Indexed: 12/08/2023]
Abstract
Neoantigen-based cancer vaccines have emerged as a promising immunotherapeutic approach to treat cancer. Nevertheless, the high degree of heterogeneity in tumors poses a significant hurdle for developing a vaccine that targets the therapeutically relevant neoantigens capable of effectively stimulating an immune response as each tumor contains numerous unique putative neoantigens. Understanding the complexities of tumor heterogeneity is crucial for the development of personalized neoantigen-based vaccines, which hold the potential to revolutionize cancer treatment and improve patient outcomes. In this review, we discuss recent advancements in the design of neoantigen-based cancer vaccines emphasizing the identification, validation, formulation, and targeting of neoantigens while addressing the challenges posed by tumor heterogeneity. The review highlights the application of cutting-edge approaches, such as single-cell sequencing and artificial intelligence to identify immunogenic neoantigens, while outlining current limitations and proposing future research directions to develop effective neoantigen-based vaccines.
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Affiliation(s)
- Saranya Pounraj
- Centre for Cell Factories and Biopolymers (CCFB), Griffith Institute for Drug Discovery, Griffith University (Nathan Campus), Brisbane, Queensland, Australia
| | - Shuxiong Chen
- Centre for Cell Factories and Biopolymers (CCFB), Griffith Institute for Drug Discovery, Griffith University (Nathan Campus), Brisbane, Queensland, Australia
| | - Linlin Ma
- Centre for Cell Factories and Biopolymers (CCFB), Griffith Institute for Drug Discovery, Griffith University (Nathan Campus), Brisbane, Queensland, Australia
- School of Environment and Science, Griffith University (Nathan Campus), Brisbane, Queensland, Australia
| | - Roberta Mazzieri
- Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia
- Peter MacCallum Department of Oncology, The University of Melbourne, Melbourne, Victoria, Australia
| | - Riccardo Dolcetti
- Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia
- Peter MacCallum Department of Oncology, The University of Melbourne, Melbourne, Victoria, Australia
- Department of Microbiology and Immunology, The University of Melbourne, Melbourne, Victoria, Australia
- Faculty of Medicine, University of Queensland, Brisbane, Queensland, Australia
| | - Bernd H A Rehm
- Centre for Cell Factories and Biopolymers (CCFB), Griffith Institute for Drug Discovery, Griffith University (Nathan Campus), Brisbane, Queensland, Australia
- Menzies Health Institute Queensland (MHIQ), Griffith University (Gold Coast Campus), Queensland, Australia
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19
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Lazarevic I, Banko A, Miljanovic D, Cupic M. Hepatitis B Surface Antigen Isoforms: Their Clinical Implications, Utilisation in Diagnosis, Prevention and New Antiviral Strategies. Pathogens 2024; 13:46. [PMID: 38251353 PMCID: PMC10818932 DOI: 10.3390/pathogens13010046] [Citation(s) in RCA: 8] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2023] [Revised: 12/27/2023] [Accepted: 01/02/2024] [Indexed: 01/23/2024] Open
Abstract
The hepatitis B surface antigen (HBsAg) is a multifunctional glycoprotein composed of large (LHB), middle (MHB), and small (SHB) subunits. HBsAg isoforms have numerous biological functions during HBV infection-from initial and specific viral attachment to the hepatocytes to initiating chronic infection with their immunomodulatory properties. The genetic variability of HBsAg isoforms may play a role in several HBV-related liver phases and clinical manifestations, from occult hepatitis and viral reactivation upon immunosuppression to fulminant hepatitis and hepatocellular carcinoma (HCC). Their immunogenic properties make them a major target for developing HBV vaccines, and in recent years they have been recognised as valuable targets for new therapeutic approaches. Initial research has already shown promising results in utilising HBsAg isoforms instead of quantitative HBsAg for correctly evaluating chronic infection phases and predicting functional cures. The ratio between surface components was shown to indicate specific outcomes of HBV and HDV infections. Thus, besides traditional HBsAg detection and quantitation, HBsAg isoform quantitation can become a useful non-invasive biomarker for assessing chronically infected patients. This review summarises the current knowledge of HBsAg isoforms, their potential usefulness and aspects deserving further research.
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Affiliation(s)
- Ivana Lazarevic
- Institute of Microbiology and Immunology, Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia; (A.B.); (D.M.); (M.C.)
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20
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Liu S, Hu M, Liu X, Liu X, Chen T, Zhu Y, Liang T, Xiao S, Li P, Ma X. Nanoparticles and Antiviral Vaccines. Vaccines (Basel) 2023; 12:30. [PMID: 38250843 PMCID: PMC10819235 DOI: 10.3390/vaccines12010030] [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: 11/22/2023] [Revised: 12/19/2023] [Accepted: 12/22/2023] [Indexed: 01/23/2024] Open
Abstract
Viruses have threatened human lives for decades, causing both chronic and acute infections accompanied by mild to severe symptoms. During the long journey of confrontation, humans have developed intricate immune systems to combat viral infections. In parallel, vaccines are invented and administrated to induce strong protective immunity while generating few adverse effects. With advancements in biochemistry and biophysics, different kinds of vaccines in versatile forms have been utilized to prevent virus infections, although the safety and effectiveness of these vaccines are diverse from each other. In this review, we first listed and described major pathogenic viruses and their pandemics that emerged in the past two centuries. Furthermore, we summarized the distinctive characteristics of different antiviral vaccines and adjuvants. Subsequently, in the main body, we reviewed recent advances of nanoparticles in the development of next-generation vaccines against influenza viruses, coronaviruses, HIV, hepatitis viruses, and many others. Specifically, we described applications of self-assembling protein polymers, virus-like particles, nano-carriers, and nano-adjuvants in antiviral vaccines. We also discussed the therapeutic potential of nanoparticles in developing safe and effective mucosal vaccines. Nanoparticle techniques could be promising platforms for developing broad-spectrum, preventive, or therapeutic antiviral vaccines.
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Affiliation(s)
- Sen Liu
- Guangzhou National Laboratory, Guangzhou International Bio-Island, Guangzhou 510005, China; (S.L.); (M.H.); (X.L.); (X.L.); (T.C.); (Y.Z.); (T.L.); (S.X.); (P.L.)
- School of Biology and Biological Engineering, South China University of Technology, Guangzhou 510006, China
| | - Meilin Hu
- Guangzhou National Laboratory, Guangzhou International Bio-Island, Guangzhou 510005, China; (S.L.); (M.H.); (X.L.); (X.L.); (T.C.); (Y.Z.); (T.L.); (S.X.); (P.L.)
- State Key Laboratory of Respiratory Disease, Guangzhou Medical University, Guangzhou 511400, China
| | - Xiaoqing Liu
- Guangzhou National Laboratory, Guangzhou International Bio-Island, Guangzhou 510005, China; (S.L.); (M.H.); (X.L.); (X.L.); (T.C.); (Y.Z.); (T.L.); (S.X.); (P.L.)
- Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou 510080, China
| | - Xingyu Liu
- Guangzhou National Laboratory, Guangzhou International Bio-Island, Guangzhou 510005, China; (S.L.); (M.H.); (X.L.); (X.L.); (T.C.); (Y.Z.); (T.L.); (S.X.); (P.L.)
| | - Tao Chen
- Guangzhou National Laboratory, Guangzhou International Bio-Island, Guangzhou 510005, China; (S.L.); (M.H.); (X.L.); (X.L.); (T.C.); (Y.Z.); (T.L.); (S.X.); (P.L.)
- State Key Laboratory of Respiratory Disease, Guangzhou Medical University, Guangzhou 511400, China
| | - Yiqiang Zhu
- Guangzhou National Laboratory, Guangzhou International Bio-Island, Guangzhou 510005, China; (S.L.); (M.H.); (X.L.); (X.L.); (T.C.); (Y.Z.); (T.L.); (S.X.); (P.L.)
| | - Taizhen Liang
- Guangzhou National Laboratory, Guangzhou International Bio-Island, Guangzhou 510005, China; (S.L.); (M.H.); (X.L.); (X.L.); (T.C.); (Y.Z.); (T.L.); (S.X.); (P.L.)
- State Key Laboratory of Respiratory Disease, Guangzhou Medical University, Guangzhou 511400, China
| | - Shiqi Xiao
- Guangzhou National Laboratory, Guangzhou International Bio-Island, Guangzhou 510005, China; (S.L.); (M.H.); (X.L.); (X.L.); (T.C.); (Y.Z.); (T.L.); (S.X.); (P.L.)
| | - Peiwen Li
- Guangzhou National Laboratory, Guangzhou International Bio-Island, Guangzhou 510005, China; (S.L.); (M.H.); (X.L.); (X.L.); (T.C.); (Y.Z.); (T.L.); (S.X.); (P.L.)
| | - Xiancai Ma
- Guangzhou National Laboratory, Guangzhou International Bio-Island, Guangzhou 510005, China; (S.L.); (M.H.); (X.L.); (X.L.); (T.C.); (Y.Z.); (T.L.); (S.X.); (P.L.)
- School of Biology and Biological Engineering, South China University of Technology, Guangzhou 510006, China
- State Key Laboratory of Respiratory Disease, Guangzhou Medical University, Guangzhou 511400, China
- Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou 510080, China
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21
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Corcorran MA, Kim HN. Strategies for Hepatitis B Virus Prevention in People Living with HIV. Curr HIV/AIDS Rep 2023; 20:451-457. [PMID: 37837570 DOI: 10.1007/s11904-023-00670-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/29/2023] [Indexed: 10/16/2023]
Abstract
PURPOSE OF REVIEW Coinfection with HIV and hepatitis B virus (HBV) is common owing to shared routes of transmission, and persons with HIV-HBV coinfection experience an accelerated progression of liver disease. Despite the widespread availability of HBV vaccination, rates of seroprotection in people living with HIV (PLWH) have historically been low. In this article, we review strategies in HBV prevention among PLWH, focusing specifically on updates in HBV vaccination and chemoprophylaxis. RECENT FINDINGS Vaccination remains the hallmark of HBV prevention, and recent studies suggest that a double dose of HBV vaccine and Heplisav-B can improve rates of seroprotection among PLWH. The use of tenofovir-containing antiretroviral therapy (ART) has similarly been shown to provide some HBV protection in PLWH; however, this protection can be lost when switching to newer tenofovir-sparing regimens, including long-acting injectables. All HBV-susceptible persons with HIV should be vaccinated against HBV, regardless of ART regimen and CD4 count.
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Affiliation(s)
- Maria A Corcorran
- Division of Allergy and Infectious Diseases, Department of Medicine, University of Washington, Seattle, WA, USA.
| | - H Nina Kim
- Division of Allergy and Infectious Diseases, Department of Medicine, University of Washington, Seattle, WA, USA
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22
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Gökengin D, Noori T, Alemany A, Bienkowski C, Liegon G, İnkaya AÇ, Carrillo J, Stary G, Knapp K, Mitja O, Molina JM. Prevention strategies for sexually transmitted infections, HIV, and viral hepatitis in Europe. THE LANCET REGIONAL HEALTH. EUROPE 2023; 34:100738. [PMID: 37927439 PMCID: PMC10625023 DOI: 10.1016/j.lanepe.2023.100738] [Citation(s) in RCA: 17] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/18/2023] [Revised: 08/26/2023] [Accepted: 09/12/2023] [Indexed: 11/07/2023]
Abstract
The current prevention efforts for STIs, HIV and viral hepatitis in the WHO European Region, especially in the Central and Eastern subregions, are hindered by healthcare disparities, data gaps, and limited resources. In this comprehensive narrative review, we aim to highlight both achievements and persisting challenges while also exploring new developments that could significantly impact the prevention of these infections in the near future. While pre-exposure prophylaxis (PrEP) for HIV has been broadly approved and implemented in 38 out of 53 countries in the region, challenges remain, including cost, limited licensing, and incomplete adherence. We explore innovative approaches like on-demand PrEP, long-acting injectable cabotegravir, and intravaginal rings that have shown promising results, alongside the use of six-monthly lenacapavir, the outcomes of which are pending. Additionally, the potential of doxycycline post-exposure prophylaxis has been discussed, revealing efficacy in reducing chlamydia and syphilis risk, but effectiveness against gonorrhoea being contingent on tetracycline resistance rates, and the need of further data to determine potential resistance development in other bacteria and its impact on the gut microbiome. We examine successful vaccination campaigns against HBV and HPV, the ongoing development of vaccines for chlamydia, syphilis, herpesvirus, and gonorrhoea, and challenges in HIV vaccine research, including lines of research with significant potential like sequential immunization, T-cell responses, and mRNA technology. This review underscores the research endeavors that pave the way for a more resilient and robust approach to combating STIs, HIV, and viral hepatitis in the region.
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Affiliation(s)
- Deniz Gökengin
- Department of Infectious Diseases and Clinical Microbiology, School of Medicine, Ege University, Izmir, Turkiye
- Ege University HIV/AIDS Practice and Research Center, Izmir, Turkiye
| | - Teymur Noori
- European Centre for Disease Prevention and Control STI, Blood-Borne Viruses and TB DPR, Stockholm, Sweden
| | - Andrea Alemany
- Skin Neglected Tropical Diseases and Sexually Transmitted Infections Section, Fight Infectious Diseases Foundation, University Hospital Germans Trias i Pujol, Badalona, Spain
| | - Carlo Bienkowski
- Department of Adults' Infectious Diseases, Medical University of Warsaw, Poland and Hospital for Infectious Diseases in Warsaw, Poland
| | - Geoffroy Liegon
- Section of Infectious Diseases and Global Health University of Chicago Medicine Chicago, Illinois, United States
| | - Ahmet Çağkan İnkaya
- Hacettepe University Faculty of Medicine Department of Infectious Diseases Ankara, Turkey
| | - Jorge Carrillo
- IrsiCaixa AIDS Research Institute, Campus Can Ruti, Badalona, Spain
- Germans Trias i Pujol Research Institute (IGTP), Campus Can Ruti, Badalona, Spain
- CIBERINFEC, Instituto de Salud Carlos IIII, Madrid, Spain
| | - Georg Stary
- Department of Dermatology, Medical University of Vienna, Vienna, Austria
| | - Katja Knapp
- Department of Dermatology, Medical University of Vienna, Vienna, Austria
| | - Oriol Mitja
- Skin Neglected Tropical Diseases and Sexually Transmitted Infections Section, Fight Infectious Diseases Foundation, University Hospital Germans Trias i Pujol, Badalona, Spain
| | - Jean-Michel Molina
- University of Paris Cité and Department of Infectious Diseases Saint-Louis and Lariboisiére Hospitals, APHP, Paris, France
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23
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Pujol FH, Toyé RM, Loureiro CL, Jaspe RC, Chemin I. Hepatitis B eradication: vaccine as a key player. Am J Transl Res 2023; 15:4971-4983. [PMID: 37692960 PMCID: PMC10492071] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2023] [Accepted: 07/26/2023] [Indexed: 09/12/2023]
Abstract
OBJECTIVE Despite the availability of a highly effective and safe vaccine against hepatitis B virus (HBV) infection for 40 years, still almost 300 million persons are estimated to be chronically infected by this virus worldwide. The World Health Organization (WHO) has proposed a plan for hepatitis elimination by 2030. However, several factors, such as the reduction and limitation in vaccination campaigns or vaccine hesitancy (VH) in some regions of the World, might have played a role in limiting the worldwide coverage of hepatitis B prophylaxis. This review aims to describe which factors, such as VH, may be hampering the WHO 2030 goal for hepatitis B eradication. METHODS The review describes the development and characteristics of the HBV vaccine, from the first plasma-derived to the recombinant one. Eventual limitations in its effectiveness and particularly VH were reviewed. RESULTS The apparent pitfalls of the HBV vaccine, such as long-term effectiveness, vaccine-escape mutants, and adverse effects, were proven not to be a concern for this vaccine. However, VH persists and was even intensified by the COVID-19 pandemic. CONCLUSIONS Many barriers still exist, such as vaccine availability, lack of awareness of the benefits of HBV vaccination, and VH. HBV VH seems to be eventually overcome in many settings with active education campaigns and information, stressing the importance of developing these strategies to achieve the 2030 goal of the WHO.
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Affiliation(s)
- Flor Helene Pujol
- Laboratorio de Virología Molecular, Centro de Microbiología y Biología Celular (CMBC), Instituto Venezolano de Investigaciones Científicas (IVIC)1020A Caracas, Venezuela
- Collegium de Lyon, Institut d’Etudes Avancées, Université Lyon 269003 Lyon, France
| | - Rayana Maryse Toyé
- Institut National de la Santé et de la Recherche Médicale (Inserm) U1052, Centre de Recherche en Cancérologie de Lyon (CRCL)151 Cours Albert Thomas, 69003 Lyon, France
| | - Carmen Luisa Loureiro
- Laboratorio de Virología Molecular, Centro de Microbiología y Biología Celular (CMBC), Instituto Venezolano de Investigaciones Científicas (IVIC)1020A Caracas, Venezuela
| | - Rossana Celeste Jaspe
- Laboratorio de Virología Molecular, Centro de Microbiología y Biología Celular (CMBC), Instituto Venezolano de Investigaciones Científicas (IVIC)1020A Caracas, Venezuela
| | - Isabelle Chemin
- Institut National de la Santé et de la Recherche Médicale (Inserm) U1052, Centre de Recherche en Cancérologie de Lyon (CRCL)151 Cours Albert Thomas, 69003 Lyon, France
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24
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Buonaguro L, Cavalluzzo B, Mauriello A, Ragone C, Tornesello AL, Buonaguro FM, Tornesello ML, Tagliamonte M. Microorganisms-derived antigens for preventive anti-cancer vaccines. Mol Aspects Med 2023; 92:101192. [PMID: 37295175 DOI: 10.1016/j.mam.2023.101192] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2023] [Revised: 05/24/2023] [Accepted: 05/29/2023] [Indexed: 06/12/2023]
Abstract
Cancer prevention is one of the aim with the highest priority in order to reduce the burden of cancer diagnosis and treatment on individuals as well as on healthcare systems. To this aim, vaccines represent the most efficient primary cancer prevention strategy. Indeed, anti-cancer immunological memory elicited by preventive vaccines might promptly expand and prevent tumor from progressing. Antigens derived from microorganisms (MoAs), represent the obvious target for developing highly effective preventive vaccines for virus-induced cancers. In this respect, the drastic reduction in cancer incidence following HBV and HPV preventive vaccines are the paradigmatic example of such evidence. More recently, experimental evidences suggest that MoAs may represent a "natural" anti-cancer preventive vaccination or can be exploited for developing vaccines to prevent cancers presenting highly homologous tumor-associated antigens (TAAs) (e.g. molecular mimicry). The present review describes the different preventive anti-cancer vaccines based on antigens derived from pathogens at the different stages of development.
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Affiliation(s)
- Luigi Buonaguro
- Innovative Immunological Models Unit, Istituto Nazionale Tumori - IRCCS - "Fond G. Pascale", Naples, Italy
| | - Beatrice Cavalluzzo
- Innovative Immunological Models Unit, Istituto Nazionale Tumori - IRCCS - "Fond G. Pascale", Naples, Italy
| | - Angela Mauriello
- Innovative Immunological Models Unit, Istituto Nazionale Tumori - IRCCS - "Fond G. Pascale", Naples, Italy
| | - Concetta Ragone
- Innovative Immunological Models Unit, Istituto Nazionale Tumori - IRCCS - "Fond G. Pascale", Naples, Italy
| | - Anna Lucia Tornesello
- Molecular Biology and Viral Oncogenesis Unit, Istituto Nazionale Tumori - IRCCS - "Fond G. Pascale", Naples, Italy
| | - Franco M Buonaguro
- Molecular Biology and Viral Oncogenesis Unit, Istituto Nazionale Tumori - IRCCS - "Fond G. Pascale", Naples, Italy
| | - Maria Lina Tornesello
- Molecular Biology and Viral Oncogenesis Unit, Istituto Nazionale Tumori - IRCCS - "Fond G. Pascale", Naples, Italy
| | - Maria Tagliamonte
- Innovative Immunological Models Unit, Istituto Nazionale Tumori - IRCCS - "Fond G. Pascale", Naples, Italy.
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25
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Butler-Laporte G, Auckland K, Noor Z, Kabir M, Alam M, Carstensen T, Wojcik GL, Chong AY, Pomilla C, Noble JA, McDevitt SL, Smits G, Wareing S, van der Klis FRM, Jeffery K, Kirkpatrick BD, Sirima S, Madhi S, Elliott A, Richards JB, Hill AVS, Duggal P, PROVIDE authors, Cryptosporidiosis Birth Cohort authors, Sandhu MS, Haque R, Petri WA, Mentzer AJ. Targeting hepatitis B vaccine escape using immunogenetics in Bangladeshi infants. MEDRXIV : THE PREPRINT SERVER FOR HEALTH SCIENCES 2023:2023.06.26.23291885. [PMID: 37425840 PMCID: PMC10327284 DOI: 10.1101/2023.06.26.23291885] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 07/11/2023]
Abstract
Hepatitis B virus (HBV) vaccine escape mutants (VEM) are increasingly described, threatening progress in control of this virus worldwide. Here we studied the relationship between host genetic variation, vaccine immunogenicity and viral sequences implicating VEM emergence. In a cohort of 1,096 Bangladeshi children, we identified human leukocyte antigen (HLA) variants associated with response vaccine antigens. Using an HLA imputation panel with 9,448 south Asian individuals DPB1*04:01 was associated with higher HBV antibody responses (p=4.5×10-30). The underlying mechanism is a result of higher affinity binding of HBV surface antigen epitopes to DPB1*04:01 dimers. This is likely a result of evolutionary pressure at the HBV surface antigen 'a-determinant' segment incurring VEM specific to HBV. Prioritizing pre-S isoform HBV vaccines may tackle the rise of HBV vaccine evasion.
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Affiliation(s)
- Guillaume Butler-Laporte
- Wellcome Centre for Human Genetics, University of Oxford, Oxford, United Kingdom
- Lady Davis Institute, Jewish General Hospital, McGill University, Montréal, Québec, Canada
- Division of Infectious Diseases, McGill University Health Centre, Montréal, Québec, Canada
| | - Kathryn Auckland
- Wellcome Centre for Human Genetics, University of Oxford, Oxford, United Kingdom
| | - Zannatun Noor
- International Centre for Diarrhoeal Disease Research, Bangladesh, Dhaka, Bangladesh
| | - Mamun Kabir
- International Centre for Diarrhoeal Disease Research, Bangladesh, Dhaka, Bangladesh
| | - Masud Alam
- International Centre for Diarrhoeal Disease Research, Bangladesh, Dhaka, Bangladesh
| | - Tommy Carstensen
- Wellcome Trust Sanger Institute, University of Cambridge, Hinxton, United Kingdom
- Queen Mary University of London, London, United Kingdom
| | - Genevieve L Wojcik
- Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA
| | - Amanda Y Chong
- Wellcome Centre for Human Genetics, University of Oxford, Oxford, United Kingdom
| | - Cristina Pomilla
- Wellcome Trust Sanger Institute, University of Cambridge, Hinxton, United Kingdom
| | - Janelle A Noble
- Children’s Hospital Oakland Research Institute, Oakland, California, USA
- Department of Pediatrics, University of California, San Francisco, California, USA
| | | | - Gaby Smits
- National Institute for Public Health and the Environment, Bilthoven, The Netherlands
| | - Susan Wareing
- Microbiology Department, John Radcliffe Hospital, Oxford University NHS Foundation Trust, Oxford, UK
| | - Fiona RM van der Klis
- National Institute for Public Health and the Environment, Bilthoven, The Netherlands
| | - Katie Jeffery
- Microbiology Department, John Radcliffe Hospital, Oxford University NHS Foundation Trust, Oxford, UK
| | - Beth D Kirkpatrick
- Department of Microbiology and Molecular Genetics, Vaccine Testing Center, University of Vermont College of Medicine, Vermont, USA
| | - Sodiomon Sirima
- Groupe de Recherche Action en Santé (GRAS) 06 BP 10248 Ouagadougou, Burkina Faso
| | - Shabir Madhi
- South African Medical Research Council Vaccines and Infectious Diseases Analytics Research Unit, University of the Witwatersrand, Johannesburg, South Africa
| | - Alison Elliott
- Department of Clinical Research, London School of Hygiene & Tropical Medicine, London, UK
- Medical Research Council/Uganda Virus Research Institute and London School of Hygiene & Tropical Medicine Uganda Research Unit, Entebbe, Uganda
| | - J Brent Richards
- Lady Davis Institute, Jewish General Hospital, McGill University, Montréal, Québec, Canada
- Department of Human Genetics, McGill University, Montréal, Québec, Canada
- 5 Prime Sciences Inc, Montreal, Quebec, Canada
- Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montréal, Québec, Canada
- Department of Twin Research, King’s College London, London, United Kingdom
| | - Adrian VS Hill
- The Jenner Institute, University of Oxford, Oxford, United Kingdom
| | - Priya Duggal
- Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA
| | | | - Manjinder S Sandhu
- Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, United Kingdom
| | - Rashidul Haque
- International Centre for Diarrhoeal Disease Research, Bangladesh, Dhaka, Bangladesh
| | - William A Petri
- Department of Medicine, Infectious Diseases and International Health, University of Virginia School of Medicine, Charlottesville, Virginia, USA
| | - Alexander J Mentzer
- Wellcome Centre for Human Genetics, University of Oxford, Oxford, United Kingdom
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26
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Pantazica AM, van Eerde A, Dobrica MO, Caras I, Ionescu I, Costache A, Tucureanu C, Steen H, Lazar C, Heldal I, Haugslien S, Onu A, Stavaru C, Branza-Nichita N, Liu Clarke J. The "humanized" N-glycosylation pathway in CRISPR/Cas9-edited Nicotiana benthamiana significantly enhances the immunogenicity of a S/preS1 Hepatitis B Virus antigen and the virus-neutralizing antibody response in vaccinated mice. PLANT BIOTECHNOLOGY JOURNAL 2023; 21:1176-1190. [PMID: 36779605 DOI: 10.1111/pbi.14028] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/05/2022] [Revised: 01/18/2023] [Accepted: 02/08/2023] [Indexed: 05/27/2023]
Abstract
The recent SARS-CoV-2 pandemic has taught the world a costly lesson about the devastating consequences of viral disease outbreaks but also, the remarkable impact of vaccination in limiting life and economic losses. Vaccination against human Hepatitis B Virus (HBV), a major human pathogen affecting 290 million people worldwide, remains a key action towards viral hepatitis elimination by 2030. To meet this goal, the development of improved HBV antigens is critical to overcome non-responsiveness to standard vaccines based on the yeast-produced, small (S) envelope protein. We have recently shown that combining relevant immunogenic determinants of S and large (L) HBV proteins in chimeric antigens markedly enhances the anti-HBV immune response. However, the demand for cost-efficient, high-quality antigens remains challenging. This issue could be addressed by using plants as versatile and rapidly scalable protein production platforms. Moreover, the recent generation of plants lacking β-1,2-xylosyltransferase and α-1,3-fucosyltransferase activities (FX-KO), by CRISPR/Cas9 genome editing, enables production of proteins with "humanized" N-glycosylation. In this study, we investigated the impact of plant N-glycosylation on the immunogenic properties of a chimeric HBV S/L vaccine candidate produced in wild-type and FX-KO Nicotiana benthamiana. Prevention of β-1,2-xylose and α-1,3-fucose attachment to the HBV antigen significantly increased the immune response in mice, as compared with the wild-type plant-produced counterpart. Notably, the antibodies triggered by the FX-KO-made antigen neutralized more efficiently both wild-type HBV and a clinically relevant vaccine escape mutant. Our study validates in premiere the glyco-engineered Nicotiana benthamiana as a substantially improved host for plant production of glycoprotein vaccines.
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Affiliation(s)
| | - André van Eerde
- NIBIO - Norwegian Institute of Bioeconomy Research, Ås, Norway
| | | | - Iuliana Caras
- "Cantacuzino" Medico-Military National Research Institute, Bucharest, Romania
| | - Irina Ionescu
- "Cantacuzino" Medico-Military National Research Institute, Bucharest, Romania
| | - Adriana Costache
- "Cantacuzino" Medico-Military National Research Institute, Bucharest, Romania
| | - Catalin Tucureanu
- "Cantacuzino" Medico-Military National Research Institute, Bucharest, Romania
| | - Hege Steen
- NIBIO - Norwegian Institute of Bioeconomy Research, Ås, Norway
| | - Catalin Lazar
- Institute of Biochemistry of the Romanian Academy, Bucharest, Romania
| | - Inger Heldal
- NIBIO - Norwegian Institute of Bioeconomy Research, Ås, Norway
| | | | - Adrian Onu
- "Cantacuzino" Medico-Military National Research Institute, Bucharest, Romania
| | - Crina Stavaru
- "Cantacuzino" Medico-Military National Research Institute, Bucharest, Romania
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Vesikari T, Langley JM, Spaans JN, Petrov I, Popovic V, Yassin-Rajkumar B, Anderson DE, Diaz-Mitoma F. The persistence of seroprotective levels of antibodies after vaccination with PreHevbrio, a 3-antigen hepatitis B vaccine. Vaccine 2023:S0264-410X(23)00528-5. [PMID: 37179167 DOI: 10.1016/j.vaccine.2023.05.010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2023] [Revised: 04/11/2023] [Accepted: 05/01/2023] [Indexed: 05/15/2023]
Abstract
Prevention of hepatitis B virus (HBV) infection by vaccination can potentially eliminate HBV-related diseases. PreHevbrio™/PreHevbri® is a 3-antigen (S, preS1, preS2) HBV vaccine (3A-HBV) recently licensed for adults in the US, EU and Canada. This study evaluated antibody persistence in a subset of fully vaccinated and seroprotected (anti-HBs ≥ 10 mIU/mL) Finnish participants from the phase 3 trial (PROTECT) of 3A-HBV versus single-antigen HBV vaccine (1A-HBV). 465/528 eligible subjects were enrolled (3A-HBV: 244; 1A-HBV: 221). Baseline characteristics were balanced. After 2.5 years, more 3A-HBV subjects remained seroprotected (88.1 % [95 %CI: 84.1,92.2]) versus 1A-HBV (72.4 % [95 %CI: 66.6,78.3)], p < 0.0001) and had higher mean anti-HBs [1382.9 mIU/mL (95 %CI: 1013.8,1751.9) versus 252.6 mIU/mL (95 %CI: 127.5,377.6), p < 0.0001]. In multiple variable logistic regression analysis including age, vaccine, initial vaccine response, sex and BMI, only higher post dose 3 (Day 196) antibody titers significantly reduced the odds of losing seroprotection.
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Affiliation(s)
- T Vesikari
- Nordic Research Network Oy, Tampere, Finland
| | - J M Langley
- Canadian Center for Vaccinology (Dalhousie University, IWK and Nova Scotia Health), Canada
| | - J N Spaans
- VBI Vaccines Inc, Cambridge, MA, United States
| | - I Petrov
- VBI Vaccines Inc, Cambridge, MA, United States
| | - V Popovic
- VBI Vaccines Inc, Cambridge, MA, United States
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28
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Talbird SE, Anderson SA, Nossov M, Beattie N, Rak AT, Diaz-Mitoma F. Cost-effectiveness of a 3-antigen versus single-antigen vaccine for the prevention of hepatitis B in adults in the United States. Vaccine 2023; 41:3506-3517. [PMID: 37147201 DOI: 10.1016/j.vaccine.2023.04.022] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2022] [Revised: 03/31/2023] [Accepted: 04/05/2023] [Indexed: 05/07/2023]
Abstract
OBJECTIVES The first 3-antigen hepatitis B vaccine was approved by the United States (US) Food and Drug Administration in November 2021 and was recommended by the Centers for Disease Control and Prevention in 2022. We estimated the cost-effectiveness of this 3-antigen vaccine (PreHevbrio™) relative to the single-antigen vaccine, Engerix-BTM, to prevent hepatitis B virus (HBV) infection among US adults. METHODS A cost-effectiveness model was developed using a combined decision-tree and Markov structure to follow 100,000 adults over their remaining lifetimes after vaccination with either the 3-antigen or single-antigen vaccine. Outcomes from societal and healthcare sector perspectives were calculated for adults aged 18-44, 45-64, and ≥65 years; adults with diabetes; and adults with obesity. Seroprotection rates were obtained from the phase3, head-to-head PROTECT trial (NCT03393754). Incidence, vaccine costs, vaccine adherence rates, direct and indirect costs, utilities, transition probabilities, and mortality were obtained from published sources. Health outcomes and costs (2020USD) were discounted 3% annually and reported by vaccine and population. One-way sensitivity and scenario analyses were conducted. RESULTS In the model, the 3-antigen vaccine led to fewer HBV infections, complications, and deaths compared with the single-antigen vaccine in all modeled populations due to higher rates and faster onset of seroprotection. Compared with the single-antigen vaccine, the 3-antigen vaccine had better health outcomes, more quality-adjusted life-years (QALYs), and lower costs in adults aged 18-64 years, adults with diabetes, and adults with obesity (dominant strategy). For adults aged ≥65 years, the 3-antigen vaccine was cost-effective compared with the single-antigen vaccine ($26,237/QALY gained) below common willingness-to-pay thresholds ($50,000-$100,000/QALY gained). In sensitivity analyses, results were sensitive to vaccine cost per dose, incidence, and age at vaccination. CONCLUSION The recently approved 3-antigen vaccine is a cost-saving or cost-effective intervention for preventing HBV infection and addressing the long-standing burden of hepatitis B among US adults.
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Affiliation(s)
- Sandra E Talbird
- RTI Health Solutions, 3040 Cornwallis Rd., Durham, NC 27709, United States.
| | - Seri A Anderson
- RTI Health Solutions, 3040 Cornwallis Rd., Durham, NC 27709, United States
| | - Misha Nossov
- VBI Vaccines Inc., 160 Second St., Floor 3, Cambridge, MA 02142, United States
| | - Nell Beattie
- VBI Vaccines Inc., 160 Second St., Floor 3, Cambridge, MA 02142, United States
| | - Aaron T Rak
- VBI Vaccines Inc., 160 Second St., Floor 3, Cambridge, MA 02142, United States
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29
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Hsu YC, Huang DQ, Nguyen MH. Global burden of hepatitis B virus: current status, missed opportunities and a call for action. Nat Rev Gastroenterol Hepatol 2023:10.1038/s41575-023-00760-9. [PMID: 37024566 DOI: 10.1038/s41575-023-00760-9] [Citation(s) in RCA: 226] [Impact Index Per Article: 113.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 02/24/2023] [Indexed: 04/08/2023]
Abstract
Chronic hepatitis B virus (HBV) infection affects about 296 million people worldwide and is the leading aetiology of cirrhosis and liver cancer globally. Major medical complications also include acute flares and extrahepatic manifestations. In addition, people living with HBV infection also experience stigma. HBV-related cirrhosis resulted in an estimated 331,000 deaths in 2019, and it is estimated that the number of deaths from HBV-related liver cancer in 2019 was 192,000, an increase from 156,000 in 2010. Meanwhile, HBV remains severely underdiagnosed and effective measures that can prevent infection and disease progression are underutilized. Birth dose coverage for HBV vaccines remains low, particularly in low-income countries or regions where HBV burden is high. Patients with HBV infection are inadequately evaluated and linked to care and are undertreated worldwide, even in high-income countries or regions. Despite the goal of the World Health Organization to eliminate viral hepatitis as a public health problem by 2030, the annual global deaths from HBV are projected to increase by 39% from 2015 to 2030 if the status quo remains. In this Review, we discuss the current status and future projections of the global burden of HBV infection. We also discuss gaps in the current care cascade and propose future directions.
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Affiliation(s)
- Yao-Chun Hsu
- Center for Liver Diseases, E-Da Hospital, Kaohsiung, Taiwan.
- School of Medicine, I-Shou University, Kaohsiung, Taiwan.
- Division of Gastroenterology, Fu-Jen Catholic University Hospital, New Taipei, Taiwan.
- Institute of Biomedical Informatics, National Yang Ming Chiao Tung University, New Taipei, Taiwan.
| | - Daniel Q Huang
- Division of Gastroenterology and Hepatology, National University Health System, Singapore, Singapore
- Department of Medicine, National University of Singapore, Singapore, Singapore
| | - Mindie H Nguyen
- Department of Medicine, Stanford University Medical Centre, Palo Alto, CA, USA.
- Department of Epidemiology and Population Health, Stanford University Medical Centre, Palo Alto, CA, USA.
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Abstract
Hepatitis B virus (HBV) infection is a major public health problem, with an estimated 296 million people chronically infected and 820 000 deaths worldwide in 2019. Diagnosis of HBV infection requires serological testing for HBsAg and for acute infection additional testing for IgM hepatitis B core antibody (IgM anti-HBc, for the window period when neither HBsAg nor anti-HBs is detected). Assessment of HBV replication status to guide treatment decisions involves testing for HBV DNA, whereas assessment of liver disease activity and staging is mainly based on aminotransferases, platelet count, and elastography. Universal infant immunisation, including birth dose vaccination is the most effective means to prevent chronic HBV infection. Two vaccines with improved immunogenicity have recently been approved for adults in the USA and EU, with availability expected to expand. Current therapies, pegylated interferon, and nucleos(t)ide analogues can prevent development of cirrhosis and hepatocellular carcinoma, but do not eradicate the virus and rarely clear HBsAg. Treatment is recommended for patients with cirrhosis or with high HBV DNA levels and active or advanced liver disease. New antiviral and immunomodulatory therapies aiming to achieve functional cure (ie, clearance of HBsAg) are in clinical development. Improved vaccination coverage, increased screening, diagnosis and linkage to care, development of curative therapies, and removal of stigma are important in achieving WHO's goal of eliminating HBV infection by 2030.
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Affiliation(s)
- Wen-Juei Jeng
- Department of Gastroenterology and Hepatology, Linkou Medical Center, Chang Gung Memorial Hospital, Taoyuan, Taiwan; College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - George V Papatheodoridis
- Academic Department of Gastroenterology, Medical School of National and Kapodistrian University of Athens, Laiko General Hospital, Athens, Greece
| | - Anna S F Lok
- Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, MI, USA.
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31
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Sucher AJ, Sucher BJ, Chahine EB. PreHevbrio: A New 3-Antigen Hepatitis B Vaccine for Adults. Ann Pharmacother 2023; 57:325-332. [PMID: 35906803 DOI: 10.1177/10600280221114469] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022] Open
Abstract
OBJECTIVE The main objective of this article is to review the immunogenicity and safety of the 3-antigen recombinant hepatitis B vaccine (3A-HepB) in adults. DATA SOURCES A literature search was performed using PubMed and Google Scholar (2000 to June 2022) with the search terms hepatitis B vaccine and 3-antigen. Other resources included the Centers for Disease Control and Prevention, conference abstracts of liver meetings, the prescribing information, and the manufacturer's website. STUDY SELECTION AND DATA EXTRACTION All English-language articles of studies assessing the immunogenicity and safety of 3A-HepB in humans were included. DATA SYNTHESIS The 3A-HepB is licensed to prevent infection caused by all known subtypes of the hepatitis B virus in adults. It contains 3 hepatitis B surface antigens. The 3A-HepB has been shown to be noninferior to a single-antigen hepatitis B vaccine (1A-HepB). It is administered intramuscularly as a 3-dose series at 0, 1, and 6 months. The most commonly reported local reactions were injection site pain and tenderness, and the most commonly reported systemic reactions were headache, fatigue, and myalgia. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE The introduction of 3A-HepB represents another step toward reducing the rates of new hepatitis B infections. However, clinical trials are needed to assess the immunogenicity of 3A-HepB in individuals at high-risk of nonresponse or low response to 1A-HepB, such as those with renal or hepatic impairment and those with altered immunocompetence. CONCLUSIONS The 3A-HepB represents another vaccine to prevent hepatitis B in adults. It is safe and immunogenic but is associated with more adverse reactions than 1A-HepB.
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Affiliation(s)
| | | | - Elias B Chahine
- Palm Beach Atlantic University, Gregory School of Pharmacy, West Palm Beach, FL, USA
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32
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Medeiros RP, Terrault NA, Mazo DF, Oliveira CP, Dodge J, Zitelli PM, Lopes MH, Carrilho FJ, Pessoa MG. Impaired anti-HBV vaccine response in non-cirrhotic chronic HCV is not overcome by double dose regimen: randomized control trial. Ann Hepatol 2023; 28:100891. [PMID: 36572211 DOI: 10.1016/j.aohep.2022.100891] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/04/2022] [Revised: 10/17/2022] [Accepted: 11/28/2022] [Indexed: 12/31/2022]
Abstract
INTRODUCTION AND OBJECTIVES Some studies suggest chronic HCV infection diminishes responses to the anti-HBV vaccine. We evaluated the efficacy of double versus standard dose HBV vaccination among HCV patients without cirrhosis. PATIENTS AND METHODS 141 adults with untreated chronic HCV were randomized to HBV vaccination with double dose (40μg) or standard dose (20μg) at 0, 1 and 6 months; 70 healthy HCV-negative patients given standard dose served as controls. Vaccine response was defined by anti-HBs ≥10 mIU/mL. RESULTS 128 patients (60 double, 68 standard doses) completed the study. Patients were of median age 52 years, 61% female, 60% fibrosis <2 of 4, and 76% genotype 1 with median 6-log 10 IU/mL HCV RNA. Overall seroprotection rate was 76.7% (95% CI: 65-87) in the 40μg versus 73.5% (95% CI: 63-84) in the 20μg dose HCV-positive groups (p =0.68) and 91.2% (95%CI:84-99) in HCV-negative controls (p =0.011 and 0.003, respectively). In multivariate logistic regression, vaccine dose (double vs. standard dose) was not associated with vaccine response (OR=0.63, p =0.33). Of 32 HCV-infected patients who were non-responders to 3- doses, 25 received the fourth dose of vaccine. The fourth dose seroconversion rate for the 40μg and 20μg groups were 45.5% and 21.4%, respectively. CONCLUSIONS In HCV-infected patients without cirrhosis, impaired responses to HBV vaccination cannot be overcome by the use of double dose HBV vaccination, but adding a fourth dose of vaccine for non-responders may be an effective strategy. Other adjuvant measures are needed to enhance seroconversion rates in these patients. TRIAL REGISTER U 1111-1264-2343 (www.ensaiosclinicos.gov.br).
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Affiliation(s)
| | | | - Daniel F Mazo
- University of São Paulo School of Medicine, São Paulo, Brazil
| | | | - Jennifer Dodge
- University of California San Francisco, San Francisco, United States
| | | | - Marta H Lopes
- University of São Paulo School of Medicine, São Paulo, Brazil
| | | | - Mário G Pessoa
- University of São Paulo School of Medicine, São Paulo, Brazil.
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Soriano V, Aguilera A, Benito R, González-Díez R, Miró E, Liendo P, Rodríguez-Diaz JC, Cabezas T, Richart A, Ramos JM, Barea L, Álvarez C, Treviño A, Gómez-Gallego F, Corral O, de Mendoza C. Susceptibility to hepatitis B virus infection in adults living in Spain. Liver Int 2023; 43:1015-1020. [PMID: 36809581 DOI: 10.1111/liv.15548] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/01/2022] [Revised: 01/11/2023] [Accepted: 02/20/2023] [Indexed: 02/23/2023]
Abstract
BACKGROUND A protective hepatitis B virus (HBV) vaccine has been available for four decades. Universal HBV vaccination of infants is recommended by the WHO since the 1990s. Furthermore, HBV immunization is advised for all adults with high-risk behaviours and no seroprotection. However, HBV vaccine coverage remains globally suboptimal. The advent of new more efficacious trivalent HBV vaccines has renewed the interest in HBV vaccination. At present, the extent of current HBV susceptibility in adults remains unknown in Spain. METHODS HBV serological markers were assessed on a large and representative sample of adults in Spain, including blood donors and individuals belonging to high-risk groups. Serum HBsAg, anti-HBc and anti-HBs were tested in specimens collected during the last couple of years. RESULTS From 13 859 consecutive adults tested at seven cities across the Spanish geography, overall 166 (1.2%) had positive HBsAg. Past HBV infection was recognized in 14% and prior vaccine immunization in 24%. Unexpectedly, 37% of blood donors and 63% of persons belonging to high-risk groups had no serum HBV markers and therefore were potentially HBV susceptible. CONCLUSION Roughly 60% of adults living in Spain seem to be HBV susceptible. Waning immunity might be more common than expected. Hence, HBV serological testing should be performed at least once in all adults regardless of risk exposures. HBV vaccine full courses or boosters should be administered to all adults lacking serological evidence of HBV protection.
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Affiliation(s)
| | - Antonio Aguilera
- Hospital Clínico Universitario de Santiago & GI-1209 USC, Santiago de Compostela, Spain
| | - Rafael Benito
- Hospital Universitario Lozano Blesa & Universidad de Zaragoza, Zaragoza, Spain
| | | | | | | | | | | | - Alberto Richart
- Centro de Transfusión de la Comunidad de Madrid, Madrid, Spain
| | | | - Luisa Barea
- Centro de Transfusión de la Comunidad de Madrid, Madrid, Spain
| | - Carmen Álvarez
- Universidad Internacional de La Rioja (UNIR), Madrid, Spain
| | - Ana Treviño
- Universidad Internacional de La Rioja (UNIR), Madrid, Spain
| | | | - Octavio Corral
- Universidad Internacional de La Rioja (UNIR), Madrid, Spain
| | - Carmen de Mendoza
- Puerta de Hierro University Hospital & Research Institute, Majadahonda, Spain
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Vesikari T, Langley JM, Popovic V, Diaz-Mitoma F. PreHevbrio: the first approved 3-antigen hepatitis B vaccine. Expert Rev Vaccines 2023; 22:1041-1054. [PMID: 37877189 DOI: 10.1080/14760584.2023.2274482] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2023] [Accepted: 10/19/2023] [Indexed: 10/26/2023]
Abstract
INTRODUCTION Hepatitis B remains a major cause of death and morbidity worldwide. Universal childhood immunization programs have been very successful, but many adults remain unprotected or are not optimally protected. PreHevbrio [Hepatitis B Vaccine (recombinant)] is a highly immunogenic 3-antigen (S/pre-S1/pre-S2) hepatitis B vaccine (3A-HBV) that recently received marketing authorization in the United States (2021), the European Union, United Kingdom (2022 - brand name PreHevbri), and Canada (2022- brand name PreHevbrio) for the prevention of infection caused by all known subtypes of the hepatitis B virus and the delta virus in adults 18 years and older. AREAS COVERED This review details the development of 3A-HBV and summarizes the results of the phase 3 clinical trials that support its immunogenicity and safety in adults. EXPERT OPINION 3A-HBV is highly immunogenic in adults of all ages, including older adults and subgroups that respond sub-optimally to conventional single S-antigen hepatitis B vaccines (1A-HBV), such as those with obesity, type 2 diabetes, and smokers. 3A-HBV provides higher seroprotection rates after each vaccination compared to conventional 1A-HBV vaccines, allowing for more rapid protection. The higher overall immunogenicity is also reflected in more durable seroprotection years after vaccination, as supported by a follow-up study to one of the phase 3 studies.
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Affiliation(s)
| | - Joanne M Langley
- IWK and Nova Scotia Health, Canadian Center for Vaccinology Dalhousie University, Halifax, Canada
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Mak LY, Beasley I, Kennedy PTF. Chronic Viral Hepatitis in Elite Athletes: Approaches to Risk Assessment, Prevention and Management. SPORTS MEDICINE - OPEN 2022; 8:123. [PMID: 36192563 PMCID: PMC9530082 DOI: 10.1186/s40798-022-00517-9] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/25/2022] [Accepted: 09/04/2022] [Indexed: 11/05/2022]
Abstract
Elite athletes who participate in contact sports are at risk of bleeding injuries, leading to transmission of blood-borne viruses including hepatitis type B, C and D (HBV, HCV and HDV) capable of causing chronic liver disease, liver failure and liver cancer. In view of the significant advances in the viral hepatitis field over the past decade, more structured approaches should be in place to screen for and manage viral hepatitis in elite athletes. HBV status should be assessed in all elite athletes, and those infected should receive nucleos(t)ide analogues for viral suppression, while uninfected individuals should receive HBV vaccination. The all-oral direct acting antivirals for HCV are highly effective and safe, thus the remaining challenge with hepatitis C is case identification and linkage to care. HDV is only found in HBV-infected individuals, which is characterized by rapid disease progression and higher rates of cirrhosis and liver cancer in infected subjects. Pegylated interferon was the mainstay of treatment for HDV infection until bulevirtide, a viral entry inhibitor, was recently approved by the European Union (EMA) and FDA in America, while multiple novel therapies are already in clinical trials as part of the HBV cure program. Overall, awareness of chronic viral hepatitis in athletes should be improved. Prevention remains the cornerstone of the management of viral hepatitis in sport coupled with rigorous disease assessment in infected individuals, and antiviral therapy where indicated.
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Affiliation(s)
- Lung-Yi Mak
- grid.4868.20000 0001 2171 1133Department of Immunobiology, Barts Liver Centre, The Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK ,grid.194645.b0000000121742757Department of Medicine, School of Clinical Medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong, China ,grid.194645.b0000000121742757State Key Laboratory of Liver Research, The University of Hong Kong, Hong Kong, China
| | - Ian Beasley
- grid.4868.20000 0001 2171 1133Centre for Sports and Exercise Medicine, Queen Mary College, London, UK
| | - Patrick T. F. Kennedy
- grid.4868.20000 0001 2171 1133Department of Immunobiology, Barts Liver Centre, The Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK
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36
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Mohsen MO, Bachmann MF. Virus-like particle vaccinology, from bench to bedside. Cell Mol Immunol 2022; 19:993-1011. [PMID: 35962190 PMCID: PMC9371956 DOI: 10.1038/s41423-022-00897-8] [Citation(s) in RCA: 123] [Impact Index Per Article: 41.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2022] [Accepted: 06/17/2022] [Indexed: 02/01/2023] Open
Abstract
Virus-like particles (VLPs) have become key tools in biology, medicine and even engineering. After their initial use to resolve viral structures at the atomic level, VLPs were rapidly harnessed to develop antiviral vaccines followed by their use as display platforms to generate any kind of vaccine. Most recently, VLPs have been employed as nanomachines to deliver pharmaceutically active products to specific sites and into specific cells in the body. Here, we focus on the use of VLPs for the development of vaccines with broad fields of indications ranging from classical vaccines against viruses to therapeutic vaccines against chronic inflammation, pain, allergy and cancer. In this review, we take a walk through time, starting with the latest developments in experimental preclinical VLP-based vaccines and ending with marketed vaccines, which earn billions of dollars every year, paving the way for the next wave of prophylactic and therapeutic vaccines already visible on the horizon.
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Affiliation(s)
- Mona O Mohsen
- Department of BioMedical Research, University of Bern, Bern, Switzerland.
- Department of Immunology RIA, University Hospital Bern, Bern, Switzerland.
- Saiba Biotech AG, Bahnhofstr. 13, CH-8808, Pfaeffikon, Switzerland.
| | - Martin F Bachmann
- Department of BioMedical Research, University of Bern, Bern, Switzerland
- Department of Immunology RIA, University Hospital Bern, Bern, Switzerland
- The Jenner Institute, University of Oxford, Oxford, UK
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37
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Di Lello FA, Martínez AP, Flichman DM. Insights into induction of the immune response by the hepatitis B vaccine. World J Gastroenterol 2022; 28:4249-4262. [PMID: 36159002 PMCID: PMC9453777 DOI: 10.3748/wjg.v28.i31.4249] [Citation(s) in RCA: 22] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/16/2022] [Revised: 05/21/2022] [Accepted: 07/25/2022] [Indexed: 02/06/2023] Open
Abstract
After more than four decades of hepatitis B virus (HBV) vaccine implementation, its safety and efficacy in preventing HBV infection have been proven and several milestones have been achieved. Most countries have included HBV immunization schedules in their health policies and progress has been made regarding universalization of the first HBV vaccine dose at birth. All of these actions have significantly contributed to reducing both the incidence of HBV infection and its related complications. However, there are still many drawbacks to overcome. The main concerns are the deficient coverage rate of the dose at birth and the large adult population that has not been reached timely by universal immunization. Additionally, the current most widely used second-generation vaccines do not induce protective immunity in 5% to 10% of the population, particularly in people over 40-years-old, obese (body mass index > 25 kg/m2), heavy smokers, and patients undergoing dialysis or infection with human immunodeficiency virus. Recently developed and approved novel vaccine formulations using more potent adjuvants or multiple antigens have shown better performance, particularly in difficult settings. These advances re-launch the expectations of achieving the World Health Organization’s objective of completing hepatitis control by 2030.
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Affiliation(s)
- Federico Alejandro Di Lello
- Microbiology, Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Investigaciones en Bacteriología y Virología Molecular, Buenos Aires C1113AAD, Argentina
- Consejo Nacional de Investigaciones Científicas y Técnicas, Buenos Aires C1425FQB, Argentina
| | - Alfredo Pedro Martínez
- Virology Section, Centro de Educación Médica e Investigaciones Clínicas Norberto Quirno “CEMIC”, Buenos Aires C1431FWO, Argentina
| | - Diego Martín Flichman
- Consejo Nacional de Investigaciones Científicas y Técnicas, Buenos Aires C1425FQB, Argentina
- Microbiology, Universidad de Buenos Aires, Instituto de Investigaciones Biomédicas en Retrovirus y Síndrome de Inmunodeficiencia Adquirida, Buenos Aires C1121ABG, Argentina
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38
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Single-dose HPV vaccine immunity: is there a role for non-neutralizing antibodies? Trends Immunol 2022; 43:815-825. [PMID: 35995705 DOI: 10.1016/j.it.2022.07.011] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2022] [Revised: 07/28/2022] [Accepted: 07/30/2022] [Indexed: 11/22/2022]
Abstract
A single dose of human papillomavirus (HPV) vaccine against HPV infection (prerequisite for cervical cancer) appears to be as efficacious as two or three doses, despite inducing lower antibody titers. Neutralizing antibodies are thought to be the primary mediator of protection, but the threshold for protection is unknown. Antibody functions beyond neutralization have not been explored for HPV vaccines. Here, we discuss the immune mechanisms of HPV vaccines, with a focus on non-neutralizing antibody effector functions. In the context of single-dose HPV vaccination where antibody is limiting, we propose that non-neutralizing antibody functions may contribute to preventing HPV infection. Understanding the immunological basis of protection for single-dose HPV vaccination will provide a rationale for implementing single-dose HPV vaccine regimens.
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Pantazica AM, Dobrica MO, Lazar C, Scurtu C, Tucureanu C, Caras I, Ionescu I, Costache A, Onu A, Clarke JL, Stavaru C, Branza-Nichita N. Efficient cellular and humoral immune response and production of virus-neutralizing antibodies by the Hepatitis B Virus S/preS116-42 antigen. Front Immunol 2022; 13:941243. [PMID: 35935966 PMCID: PMC9354405 DOI: 10.3389/fimmu.2022.941243] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2022] [Accepted: 06/27/2022] [Indexed: 11/13/2022] Open
Abstract
Despite the availability of improved antiviral therapies, infection with Hepatitis B virus (HBV) remains a3 significant health issue, as a curable treatment is yet to be discovered. Current HBV vaccines relaying on the efficient expression of the small (S) envelope protein in yeast and the implementation of mass vaccination programs have clearly contributed to containment of the disease. However, the lack of an efficient immune response in up to 10% of vaccinated adults, the controversies regarding the seroprotection persistence in vaccine responders and the emergence of vaccine escape virus mutations urge for the development of better HBV immunogens. Due to the critical role played by the preS1 domain of the large (L) envelope protein in HBV infection and its ability to trigger virus neutralizing antibodies, including this protein in novel vaccine formulations has been considered a promising strategy to overcome the limitations of S only-based vaccines. In this work we aimed to combine relevant L and S epitopes in chimeric antigens, by inserting preS1 sequences within the external antigenic loop of S, followed by production in mammalian cells and detailed analysis of their antigenic and immunogenic properties. Of the newly designed antigens, the S/preS116–42 protein assembled in subviral particles (SVP) showed the highest expression and secretion levels, therefore, it was selected for further studies in vivo. Analysis of the immune response induced in mice vaccinated with S/preS116–42- and S-SVPs, respectively, demonstrated enhanced immunogenicity of the former and its ability to activate both humoral and cellular immune responses. This combined activation resulted in production of neutralizing antibodies against both wild-type and vaccine-escape HBV variants. Our results validate the design of chimeric HBV antigens and promote the novel S/preS1 protein as a potential vaccine candidate for administration in poor-responders to current HBV vaccines.
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Affiliation(s)
- Ana-Maria Pantazica
- Department of Viral Glycoproteins, Institute of Biochemistry of the Romanian Academy, Bucharest, Romania
| | - Mihaela-Olivia Dobrica
- Department of Viral Glycoproteins, Institute of Biochemistry of the Romanian Academy, Bucharest, Romania
| | - Catalin Lazar
- Department of Viral Glycoproteins, Institute of Biochemistry of the Romanian Academy, Bucharest, Romania
| | - Cristina Scurtu
- Department of Viral Glycoproteins, Institute of Biochemistry of the Romanian Academy, Bucharest, Romania
| | - Catalin Tucureanu
- Immunology Laboratory, “Cantacuzino” Medico-Military National Research Institute, Bucharest, Romania
| | - Iuliana Caras
- Immunology Laboratory, “Cantacuzino” Medico-Military National Research Institute, Bucharest, Romania
| | - Irina Ionescu
- Immunology Laboratory, “Cantacuzino” Medico-Military National Research Institute, Bucharest, Romania
| | - Adriana Costache
- Immunology Laboratory, “Cantacuzino” Medico-Military National Research Institute, Bucharest, Romania
| | - Adrian Onu
- Immunology Laboratory, “Cantacuzino” Medico-Military National Research Institute, Bucharest, Romania
| | - Jihong Liu Clarke
- Division of Biotechnology and Plant Health, NIBIO - Norwegian Institute for Bioeconomy Research, Ås, Norway
| | - Crina Stavaru
- Immunology Laboratory, “Cantacuzino” Medico-Military National Research Institute, Bucharest, Romania
- *Correspondence: Norica Branza-Nichita, ; Crina Stavaru,
| | - Norica Branza-Nichita
- Department of Viral Glycoproteins, Institute of Biochemistry of the Romanian Academy, Bucharest, Romania
- *Correspondence: Norica Branza-Nichita, ; Crina Stavaru,
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40
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Romano’ L, Zanetti AR. Hepatitis B Vaccination: A Historical Overview with a Focus on the Italian Achievements. Viruses 2022; 14:1515. [PMID: 35891495 PMCID: PMC9320049 DOI: 10.3390/v14071515] [Citation(s) in RCA: 23] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2022] [Revised: 07/08/2022] [Accepted: 07/08/2022] [Indexed: 11/16/2022] Open
Abstract
Vaccination is the most effective way to control and prevent acute and chronic hepatitis B, including cirrhosis and HCC, on a global scale. According to WHO recommendations, 190 countries in the world have introduced hepatitis B vaccination into their national childhood immunization programs with an excellent profile of safety, immunogenicity, and effectiveness. Following vaccination, seroprotection rates are close to 100% in healthy children and over 95% in healthy adults. Persistence of anti-HBs is related to the antibody peak achieved after vaccination. The peak is higher the longer the antibody duration is. Loss of anti-HBs does not necessarily mean loss of immunity since most vaccinated individuals retain immune memory for HBsAg and rapidly develop strong anamnestic responses when boosted. Evidence indicates that the duration of protection can persist for at least 35 years after priming. Hence, booster doses of vaccines are currently not recommended to sustain long-term immunity in healthy vaccinated individuals. In Italy, vaccination against hepatitis B is met with success. In 2020, Italy became one of the first countries in Europe to be validated for achieving the WHO regional hepatitis B control targets.
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Affiliation(s)
- Luisa Romano’
- Dipartimento di Scienze Biomediche per la Salute, Università degli Studi, 20133 Milano, Italy;
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41
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Abouqal R, Beji M, Chakroun M, Marhoum El Filali K, Rammaoui J, Zaghden H. Trends in Adult and Elderly Vaccination: Focus on Vaccination Practices in Tunisia and Morocco. Front Public Health 2022; 10:903376. [PMID: 35844850 PMCID: PMC9286557 DOI: 10.3389/fpubh.2022.903376] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2022] [Accepted: 06/09/2022] [Indexed: 11/25/2022] Open
Abstract
Vaccine preventable diseases (VPDs) are a prevailing concern among the adult population, despite availability of vaccines. Unlike pediatric vaccination programs, adult vaccination programs lack the required reach, initiative, and awareness. Clinical studies and real-world data have proven that vaccines effectively reduce the disease burden of VPDs and increase life expectancy. In Tunisia and Morocco, the national immunization program (NIP) focuses more on pediatric vaccination and have limited vaccination programs for adults. However, some vaccination campaigns targeting adults are organized. For example, influenza vaccination campaigns prioritizing at risk adults which includes healthcare professionals, elderly, and patients with comorbidities. Women of childbearing age who have never been vaccinated or whose information is uncertain are recommended to receive tetanus vaccination. Tunisia NIP recommends rubella vaccine mainly for women of childbearing age, while in Morocco, national vaccination campaigns were organized for girls and women (up to 24 years of age) to eliminate rubella. Further, travelers from both countries are recommended to follow all requirements and recommendations in the travel destination. The objective of this manuscript is to provide an overview of the global disease burden of common VPDs including (but not limited to) meningococcal diseases, pneumococcal diseases, hepatitis, and influenza. The review also provides an overview of clinical data and guidelines/recommendations on adult vaccination practices, with special focus on Tunisia and Morocco. Some European and North American countries have concrete recommendations and strategies for adult vaccination to keep the VPDs in check. In Morocco and Tunisia, although, there are sporadic adult vaccination initiatives, the efforts still need upscaling and endorsements to boost vaccination awareness and uptake. There is a need to strengthen strategies in both countries to understand the disease burden and spread awareness. Additional studies are needed to generate economic evidence to support cost-effectiveness of vaccines. Integration of private and public healthcare systems may further improve vaccination uptake in adults.
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Affiliation(s)
- Redouane Abouqal
- Laboratory of Biostatistics, Clinical and Epidemiological Research, Faculty of Medicine and Pharmacy, Mohammed V University in Rabat, Rabat, Morocco
- Acute Medical Unit, Ibn Sina University Hospital, Rabat, Morocco
| | - Maher Beji
- Department of Internal Medicine, Military Hospital Bizerte, Bizerte, Tunisia
- Faculty of Medicine of Tunis, University El Manar, Tunis, Tunisia
- Tunisian Society of Tropical Medicine and Travel, Tunis, Tunisia
| | - Mohamed Chakroun
- Infectious Diseases Department, University Hospital, Monastir, Tunisia
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Jacobson IM, Brown RS, McMahon BJ, Perrillo RP, Gish R. An Evidence-based Practical Guide to Vaccination for Hepatitis B Virus. J Clin Gastroenterol 2022; 56:478-492. [PMID: 35389923 DOI: 10.1097/mcg.0000000000001695] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/10/2022]
Abstract
The hepatitis B virus (HBV) is highly infectious, with over 292 million chronically infected people worldwide and up to 2.4 million in the United States. Following infection, clinically silent liver damage can ensue, but symptoms or signs of advanced disease, including cirrhosis and hepatocellular carcinoma, can take decades to emerge. HBV has the heaviest public health burden of all hepatitis viruses and has now surpassed other major communicable diseases (eg, HIV, diarrheal disease, malaria, tuberculosis) as a leading cause of death globally. Preventing transmission is essential, and efforts are in place to reinforce screening, vaccination, and routine follow-up. Three safe and effective vaccines are available in the United States and other countries for HBV prevention, and the benefits of vaccination in preventing infection and its sequelae have been substantiated. For the first time in over 25 years, a new Food and Drug Administration-approved vaccine is available that offers a high degree of immunogenicity after 2, rather than 3, injections. Persistent challenges include the underutilization of vaccination, choice of vaccine, incomplete vaccinations, varying needs in different populations, management of nonresponders or those with undocumented or incompletely documented vaccination courses, and questions about whether and when booster injections may be needed. A panel of US academic hepatologists with expertise and experience in preventing and managing HBV infection have collaborated to write this practical clinical paper intended to guide clinicians in vaccinating for HBV and address questions that regularly arise in the clinic.
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Affiliation(s)
| | - Robert S Brown
- Division of Gastroenterology and Hepatology, Weill Cornell Medicine, New York, NY
| | - Brian J McMahon
- University of Washington, Seattle, WA
- University of Alaska
- Alaska Native Tribal Health Consortium, Anchorage, AK
| | - Robert P Perrillo
- Hepatology Division, Baylor Scott and White Medical Center, University of Texas Southwestern, Dallas, TX
| | - Robert Gish
- Loma Linda University, Loma Linda
- UCSD Skaggs School of Pharmacy and Pharmaceutical Sciences, La Jolla, CA
- University of Nevada Las Vegas and Reno Schools of Medicine, Las Vegas, NV
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