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Younas S, Bukhari DA, Bibi Z, Ullah A, Rehman A. Impact of multistrain probiotics on growth performance, immune response, and gut morphometry in broiler chicken Gallus gallus domesticus. Poult Sci 2025; 104:105026. [PMID: 40101512 PMCID: PMC11960641 DOI: 10.1016/j.psj.2025.105026] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2024] [Revised: 03/10/2025] [Accepted: 03/11/2025] [Indexed: 03/20/2025] Open
Abstract
The objective of this investigation was to examine the impact of four lab-isolated probiotics Enterococcus faecium (OR563785.1), Weissella confusa (OR563786.1), Weissella cibaria (OQ543569.1), Lactiplantibacillus plantarum (OQ689085.1) in 1:1:1:1 of CFU dilution as multistrain probiotics (MSP) regarding growth performance, haemato-biochemical indices and immune function in broilers. Ninety uniformly weighed broilers were divided into five groups at random with (n = 18/group). NC: negative control (basal diet); PC: commercial probiotic, G1: MSP supplemented, G2: MSP + vaccinated, G3: (vaccinated). Blood samples were collected at 42 days of age to assess immunological, haemato-biochemical parameters, and intestinal morphometry. Compared to the group of negative control, the broiler chicks' body weight was considerably (p < 0.05) higher in MSP-treated groups (G1, G2). This study found that, as compared to the NC, there was a substantial rise (p < 0.05) in RBC and hemoglobin in the probiotic-supplemented bird group. The results indicated that cholesterol and triglyceride remarkably decreased compared to control in probiotic-treated groups. There was no discernible change in the enzyme activity of ALT, AST, and ALP across the groups (p > 0.05). The findings indicated higher levels of immunoglobulin and interleukins in the MSP group than in the control (NC). The villus's height to crypt depth ratio was higher in the MSP groups (G1, G2) in contrast with the PC group (p < 0.05). The haemagglutination inhibition test (HI) revealed that the probiotic-treated groups had greater New Castle disease virus (NDV) antibodies than the other groups. The humoral response to live NDV vaccinations may be enhanced by multistrain probiotics. These results revealed MSP significantly affected growth performance, haematobiochemical parameters, and immunity through alteration in intestinal morphology which helps in nutrient uptake.
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Affiliation(s)
- Samina Younas
- Institute of Zoology, Government College University, Lahore, Pakistan
| | | | - Zuhra Bibi
- Institute of Zoology, Government College University, Lahore, Pakistan
| | - Arif Ullah
- Institute of Zoology, Government College University, Lahore, Pakistan
| | - Abdul Rehman
- Institute of Microbiology and Molecular Genetics, University of the Punjab, Lahore, Pakistan.
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Rahim MA, Seo H, Barman I, Hossain MS, Shuvo MSH, Song HY. Insights into Autophagy in Microbiome Therapeutic Approaches for Drug-Resistant Tuberculosis. Cells 2025; 14:540. [PMID: 40214493 PMCID: PMC11989032 DOI: 10.3390/cells14070540] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2025] [Revised: 03/23/2025] [Accepted: 04/02/2025] [Indexed: 04/14/2025] Open
Abstract
Tuberculosis, primarily caused by Mycobacterium tuberculosis, is an airborne lung disease and continues to pose a significant global health threat, resulting in millions of deaths annually. The current treatment for tuberculosis involves a prolonged regimen of antibiotics, which leads to complications such as recurrence, drug resistance, reinfection, and a range of side effects. This scenario underscores the urgent need for novel therapeutic strategies to combat this lethal pathogen. Over the last two decades, microbiome therapeutics have emerged as promising next-generation drug candidates, offering advantages over traditional medications. In 2022, the Food and Drug Administration approved the first microbiome therapeutic for recurrent Clostridium infections, and extensive research is underway on microbiome treatments for various challenging diseases, including metabolic disorders and cancer. Research on microbiomes concerning tuberculosis commenced roughly a decade ago, and the scope of this research has broadened considerably over the last five years, with microbiome therapeutics now viewed as viable options for managing drug-resistant tuberculosis. Nevertheless, the understanding of their mechanisms is still in its infancy. Although autophagy has been extensively studied in other diseases, research into its role in tuberculosis is just beginning, with preliminary developments in progress. Against this backdrop, this comprehensive review begins by succinctly outlining tuberculosis' characteristics and assessing existing treatments' strengths and weaknesses, followed by a detailed examination of microbiome-based therapeutic approaches for drug-resistant tuberculosis. Additionally, this review focuses on establishing a basic understanding of microbiome treatments for tuberculosis, mainly through the lens of autophagy as a mechanism of action. Ultimately, this review aims to contribute to the foundational comprehension of microbiome-based therapies for tuberculosis, thereby setting the stage for the further advancement of microbiome therapeutics for drug-resistant tuberculosis.
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Affiliation(s)
- Md Abdur Rahim
- Department of Microbiology and Immunology, School of Medicine, Soonchunhyang University, 31, Suncheonhyang 6-gil, Dongnam-gu, Cheonan-si 31151, Republic of Korea
- Human Microbiome Medical Research Center (HM·MRC), School of Medicine, Soonchunhyang University, 22, Soonchunhyang-ro, Sinchang-myeon, Asan-si 31538, Republic of Korea
| | - Hoonhee Seo
- Human Microbiome Medical Research Center (HM·MRC), School of Medicine, Soonchunhyang University, 22, Soonchunhyang-ro, Sinchang-myeon, Asan-si 31538, Republic of Korea
- Probiotics Microbiome Commercialization Research Center (PMC), Soonchunhyang University, 22, Soonchunhyang-ro, Sinchang-myeon, Asan-si 31538, Republic of Korea
| | - Indrajeet Barman
- Department of Microbiology and Immunology, School of Medicine, Soonchunhyang University, 31, Suncheonhyang 6-gil, Dongnam-gu, Cheonan-si 31151, Republic of Korea
- Human Microbiome Medical Research Center (HM·MRC), School of Medicine, Soonchunhyang University, 22, Soonchunhyang-ro, Sinchang-myeon, Asan-si 31538, Republic of Korea
| | - Mohammed Solayman Hossain
- Department of Microbiology and Immunology, School of Medicine, Soonchunhyang University, 31, Suncheonhyang 6-gil, Dongnam-gu, Cheonan-si 31151, Republic of Korea
- Human Microbiome Medical Research Center (HM·MRC), School of Medicine, Soonchunhyang University, 22, Soonchunhyang-ro, Sinchang-myeon, Asan-si 31538, Republic of Korea
| | - Md Sarower Hossen Shuvo
- Department of Microbiology and Immunology, School of Medicine, Soonchunhyang University, 31, Suncheonhyang 6-gil, Dongnam-gu, Cheonan-si 31151, Republic of Korea
- Human Microbiome Medical Research Center (HM·MRC), School of Medicine, Soonchunhyang University, 22, Soonchunhyang-ro, Sinchang-myeon, Asan-si 31538, Republic of Korea
| | - Ho-Yeon Song
- Department of Microbiology and Immunology, School of Medicine, Soonchunhyang University, 31, Suncheonhyang 6-gil, Dongnam-gu, Cheonan-si 31151, Republic of Korea
- Human Microbiome Medical Research Center (HM·MRC), School of Medicine, Soonchunhyang University, 22, Soonchunhyang-ro, Sinchang-myeon, Asan-si 31538, Republic of Korea
- Probiotics Microbiome Commercialization Research Center (PMC), Soonchunhyang University, 22, Soonchunhyang-ro, Sinchang-myeon, Asan-si 31538, Republic of Korea
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Wang Y, Waters AK, Basalirwa G, Ssetaala A, Mpendo J, Namuniina A, Keneema E, Kiiza D, Kyosiimire-Lugemwa J, Mayanja Y, Okech B, Kiwuwa-Muyingo S. Impact of Schistosoma mansoni Infection on the Gut Microbiome and Hepatitis B Vaccine Immune Response in Fishing Communities of Lake Victoria, Uganda. Vaccines (Basel) 2025; 13:375. [PMID: 40333219 PMCID: PMC12030974 DOI: 10.3390/vaccines13040375] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2025] [Revised: 03/19/2025] [Accepted: 03/25/2025] [Indexed: 05/09/2025] Open
Abstract
OBJECTIVE Schistosoma mansoni (S. mansoni) infection is endemic in Ugandan fishing communities. We investigated its potential impact on Hepatitis B (Hep B) vaccine responses and its role in mediating the association between the gut microbiome and long-term effectiveness of the vaccine. METHODS Participants were tested for S. mansoni infections at baseline and received the Hep B vaccine at baseline, month 1, and month 6. Those with infections were treated. Stool samples were collected at baseline and analyzed using 16S rRNA sequencing. The Wilcoxon rank-sum test was used to compare alpha diversity between groups. A linear regression model was applied to estimate the association between one-year Hep B vaccine responses and the baseline gut microbiome by infection status, adjusting for age and sex. RESULTS A total of 107 participants were included (44 from the fishing community and 63 from the Kampala community). There was no significant difference in microbiome composition by location or infection status at baseline or discharge. In the linear regression analysis, S. mansoni infection (β = 1.24, p = 0.025) and a higher alpha diversity (β = 0.001, p = 0.07) were associated with higher Hep B vaccine responses, while older age was associated with a lower Hep B vaccine response (β = -0.06, p = 0.0013). CONCLUSIONS S. mansoni infection status before vaccination may modify the association between the gut microbiome and Hep B vaccine response. Potential interventions could focus on infection control as well as improving microbiome richness before implementing vaccine programs in fishing communities.
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Affiliation(s)
- Yan Wang
- Public and Population Health, School of Dentistry, University of California, Los Angeles, CA 90095, USA
| | - Ariana K. Waters
- School of Public Health, University of California, Berkeley, CA 94704, USA
| | | | - Ali Ssetaala
- UVRI-IAVI HIV Vaccine Program, Entebbe P.O. Box 49, Uganda
| | - Juliet Mpendo
- UVRI-IAVI HIV Vaccine Program, Entebbe P.O. Box 49, Uganda
| | | | - Emily Keneema
- UVRI-IAVI HIV Vaccine Program, Entebbe P.O. Box 49, Uganda
| | - David Kiiza
- UVRI-IAVI HIV Vaccine Program, Entebbe P.O. Box 49, Uganda
| | - Jacqueline Kyosiimire-Lugemwa
- Medical Research Council/Uganda Virus Research Institute and London School of Hygiene and Tropical Medicine (MRC/UVRI & LSHTM) Uganda Research Unit, P.O. Box 49, Plot 51-59 Nakiwogo Road, Entebbe 256, Uganda
- University of Kisubi, Faculty of Health Science and Department of Biomedical Sciences, Entebbe P.O. Box 182, Uganda
| | - Yunia Mayanja
- Medical Research Council/Uganda Virus Research Institute and London School of Hygiene and Tropical Medicine (MRC/UVRI & LSHTM) Uganda Research Unit, P.O. Box 49, Plot 51-59 Nakiwogo Road, Entebbe 256, Uganda
| | - Brenda Okech
- UVRI-IAVI HIV Vaccine Program, Entebbe P.O. Box 49, Uganda
| | - Sylvia Kiwuwa-Muyingo
- African Population & Health Research Center (APHRC), Nairobi Kenya P.O. Box 10787-00100, Kenya
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Loddo F, Laganà P, Rizzo CE, Calderone SM, Romeo B, Venuto R, Maisano D, Fedele F, Squeri R, Nicita A, Nirta A, Genovese G, Bartucciotto L, Genovese C. Intestinal Microbiota and Vaccinations: A Systematic Review of the Literature. Vaccines (Basel) 2025; 13:306. [PMID: 40266208 PMCID: PMC11946530 DOI: 10.3390/vaccines13030306] [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: 02/10/2025] [Revised: 03/04/2025] [Accepted: 03/05/2025] [Indexed: 04/24/2025] Open
Abstract
Background: Vaccination constitutes a low-cost, safe, and efficient public health measure that can help prevent the spread of infectious diseases and benefit the community. The fact that vaccination effectiveness varies among populations, and that the causes of this are still unclear, indicates that several factors are involved and should be thoroughly examined. The "intestinal microbiota" is the most crucial of these elements. Numerous clinical studies demonstrate the intestinal microbiota's significance in determining the alleged "immunogenicity" and efficacy of vaccines. This systematic review aimed to review all relevant scientific literature and highlight the role of intestinal microbiota in COVID-19, Salmonella typhi, Vibrio cholerae, and rotavirus vaccinations. Materials and Methods: The MESH terms "vaccines" and "microbiota" were used to search the major scientific databases PubMed, SciVerse Scopus, Web of Knowledge, and the Cochrane Central Register of Controlled Clinical Trials. Results: Between February 2024 and October 2024, the analysis was conducted using electronic databases, yielding a total of 235 references. Finally, 24 RCTs were chosen after meeting all inclusion criteria: eight studies of COVID-19, two studies of Salmonella typhi, three studies of Vibrio cholerae, and eleven studies of rotavirus. Only six of these demonstrated good study quality with a Jadad score of three or four. Conclusions: According to the review's results, the intestinal microbiota surely plays a role in vaccinations' enhanced immunogenicity, especially in younger people. As it is still unclear what mechanisms underlie this effect, more research is needed to better understand the role of the intestinal microbiota.
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Affiliation(s)
| | | | | | | | | | | | | | | | | | | | | | - Giovanni Genovese
- Department of Biomedical, Dental and Morphological and Functional Imaging Sciences, University of Messina, 98122 Messina, Italy; (F.L.); (P.L.); (C.E.R.); (S.M.C.); (B.R.); (R.V.); (D.M.); (F.F.); (R.S.); (A.N.); (A.N.); (L.B.)
| | | | - Cristina Genovese
- Department of Biomedical, Dental and Morphological and Functional Imaging Sciences, University of Messina, 98122 Messina, Italy; (F.L.); (P.L.); (C.E.R.); (S.M.C.); (B.R.); (R.V.); (D.M.); (F.F.); (R.S.); (A.N.); (A.N.); (L.B.)
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Mojgani N, Ashique S, Moradi M, Bagheri M, Garg A, Kaushik M, Hussain MS, Yasmin S, Ansari MY. Gut Microbiota and Postbiotic Metabolites: Biotic Intervention for Enhancing Vaccine Responses and Personalized Medicine for Disease Prevention. Probiotics Antimicrob Proteins 2025. [DOI: 10.1007/s12602-025-10477-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/30/2025] [Indexed: 05/04/2025]
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Vasquez R, Song JH, Mendoza RM, Hwang I, Bagon BB, Engstrand L, Valeriano VD, Kang D. Oral Immunisation With Non-GMO Surface Displayed SARS-CoV-2 Spike Epitopes on Bacteria-Like Particles Provokes Robust Humoral and Cellular Immune Responses, and Modulated the Gut Microbiome in Mice. Microb Biotechnol 2025; 18:e70073. [PMID: 39797809 PMCID: PMC11724470 DOI: 10.1111/1751-7915.70073] [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: 09/10/2024] [Revised: 12/11/2024] [Accepted: 12/18/2024] [Indexed: 01/13/2025] Open
Abstract
The coronavirus disease 2019 (COVID-19) is a fatal disease caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). To date, several vaccines have been developed to combat the spread of this virus. Mucosal vaccines using food-grade bacteria, such as Lactobacillus spp., are promising strategies for developing safe and effective vaccines against SARS-CoV-2. In this study, we designed a non-GMO surface-displayed SARS-CoV-2 spike S1 epitope on Limosilactobacillus fermentum-derived bacteria-like particles (BLPs). After that, we evaluated its efficacy to induce immune responses in immunocompetent mice. Moreover, we examined the influence of oral immunisation on the gut microbiome and microbiota metabolites. Twenty-eight 6-week-old male C57BL/6 mice were orally immunised with the following: PBS (control), Lm. fermentum-derived BLPs only, BLPs displaying SARS-CoV-2 spike S1-2, or BLPs displaying SARS-CoV-2 spike S1-3 epitopes. Our results showed that mucosal immunisation of mice with surface-displayed SARS-CoV-2 spike epitopes provoked high-level secretory IgA and systemic IgG production. Moreover, the immunisation exhibited a Th1-like immune response, characterised by an elevated IgG2a-to-IgG1 ratio and high antiviral IFN-γ production. In addition, we observed gut microbiome modulation and increased butyrate production in immunised mice. Overall, the use of Lm. fermentum-derived BLPs and the anchor CshA to display SARS-CoV-2 spike S1epitopes is a promising novel strategy in developing a cost-effective, non-GMO mucosal vaccine alternative against SARS-CoV-2.
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Affiliation(s)
- Robie Vasquez
- Department of Animal BiotechnologyDankook UniversityCheonanKorea
| | - Ji Hoon Song
- Department of Animal BiotechnologyDankook UniversityCheonanKorea
| | | | - In‐Chan Hwang
- Department of Animal BiotechnologyDankook UniversityCheonanKorea
- Department of Microbiology, Tumor and Cell Biology, Centre for Translational Microbiome Research (CTMR)Karolinska InstitutetStockholmSweden
| | | | - Lars Engstrand
- Department of Microbiology, Tumor and Cell Biology, Centre for Translational Microbiome Research (CTMR)Karolinska InstitutetStockholmSweden
| | - Valerie Diane Valeriano
- Department of Microbiology, Tumor and Cell Biology, Centre for Translational Microbiome Research (CTMR)Karolinska InstitutetStockholmSweden
| | - Dae‐Kyung Kang
- Department of Animal BiotechnologyDankook UniversityCheonanKorea
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Ardura-Garcia C, Curtis N, Zimmermann P. Systematic review of the impact of intestinal microbiota on vaccine responses. NPJ Vaccines 2024; 9:254. [PMID: 39706841 DOI: 10.1038/s41541-024-01000-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2024] [Accepted: 10/17/2024] [Indexed: 12/23/2024] Open
Abstract
The intestinal microbiota plays a critical role in host immunity and might contribute to the significant variation between individuals' vaccine responses. A systematic search was done using MEDLINE and Embase to identify original human studies investigating the association between intestinal microbiota composition and humoral and cellular vaccine responses. In total, 30 publications (26 studies, 14 in infants, 12 in adults), were included. Of these, 26 publications found an association between intestinal microbiota composition and vaccine responses. A beneficial effect of Actynomycetota (particularly Bifidobacterium) and a detrimental effect of Pseudomonadota (particularly Gammaproteobacteria) were observed across studies. Study designs were highly heterogenous, with variation in vaccine type, outcome measure, timing of stool analysis and analysis methods. Overall, studies support the concept that the composition of the intestinal microbiota influences vaccine responses. Further adequately powered studies are needed to confirm this association and inform potential microbiota-targeted interventions to optimise vaccine responses.
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Affiliation(s)
- Cristina Ardura-Garcia
- Department of Paediatrics, Fribourg Hospital, Fribourg, Switzerland
- Cambodia Oxford Medical Research Unit, Angkor Hospital for Children, Siem Reap, Cambodia
| | - Nigel Curtis
- Department of Paediatrics, The University of Melbourne, Parkville, VIC, Australia
- Infectious Diseases Research Group, Murdoch Children's Research Institute, Parkville, VIC, Australia
- Infectious Diseases Unit, The Royal Children's Hospital Melbourne, Parkville, VIC, Australia
| | - Petra Zimmermann
- Department of Paediatrics, Fribourg Hospital, Fribourg, Switzerland.
- Department of Paediatrics, The University of Melbourne, Parkville, VIC, Australia.
- Infectious Diseases Research Group, Murdoch Children's Research Institute, Parkville, VIC, Australia.
- Department for Community Health, Faculty of Science and Medicine, University of Fribourg, Fribourg, Switzerland.
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Abeltino A, Hatem D, Serantoni C, Riente A, De Giulio MM, De Spirito M, De Maio F, Maulucci G. Unraveling the Gut Microbiota: Implications for Precision Nutrition and Personalized Medicine. Nutrients 2024; 16:3806. [PMID: 39599593 PMCID: PMC11597134 DOI: 10.3390/nu16223806] [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: 10/08/2024] [Revised: 10/31/2024] [Accepted: 11/05/2024] [Indexed: 11/29/2024] Open
Abstract
Recent studies have shown a growing interest in the complex relationship between the human gut microbiota, metabolism, and overall health. This review aims to explore the gut microbiota-host association, focusing on its implications for precision nutrition and personalized medicine. The objective is to highlight how gut microbiota modulate metabolic and immune functions, contributing to disease susceptibility and wellbeing. The review synthesizes recent research findings, analyzing key studies on the influence of gut microbiota on lipid and carbohydrate metabolism, intestinal health, neurobehavioral regulation, and endocrine signaling. Data were drawn from both experimental and clinical trials examining microbiota-host interactions relevant to precision nutrition. Our findings highlight the essential role of gut microbiota-derived metabolites in regulating host metabolism, including lipid and glucose pathways. These metabolites have been found to influence immune responses and gut barrier integrity. Additionally, the microbiota impacts broader physiological processes, including neuroendocrine regulation, which could be crucial for dietary interventions. Therefore, understanding the molecular mechanisms of dietary-microbiota-host interactions is pivotal for advancing personalized nutrition strategies. Tailored dietary recommendations based on individual gut microbiota compositions hold promise for improving health outcomes, potentially revolutionizing future healthcare approaches across diverse populations.
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Affiliation(s)
- Alessio Abeltino
- Metabolic Intelligence Lab, Department of Neuroscience, Università Cattolica del Sacro Cuore, Largo Francesco Vito, 1, 00168 Rome, Italy; (A.A.); (D.H.); (C.S.); (A.R.); (M.M.D.G.); (M.D.S.)
- UOC Physics for Life Sciences, Fondazione Policlinico Universitario “A. Gemelli” IRCCS, 00168 Rome, Italy
| | - Duaa Hatem
- Metabolic Intelligence Lab, Department of Neuroscience, Università Cattolica del Sacro Cuore, Largo Francesco Vito, 1, 00168 Rome, Italy; (A.A.); (D.H.); (C.S.); (A.R.); (M.M.D.G.); (M.D.S.)
- UOC Physics for Life Sciences, Fondazione Policlinico Universitario “A. Gemelli” IRCCS, 00168 Rome, Italy
| | - Cassandra Serantoni
- Metabolic Intelligence Lab, Department of Neuroscience, Università Cattolica del Sacro Cuore, Largo Francesco Vito, 1, 00168 Rome, Italy; (A.A.); (D.H.); (C.S.); (A.R.); (M.M.D.G.); (M.D.S.)
- UOC Physics for Life Sciences, Fondazione Policlinico Universitario “A. Gemelli” IRCCS, 00168 Rome, Italy
| | - Alessia Riente
- Metabolic Intelligence Lab, Department of Neuroscience, Università Cattolica del Sacro Cuore, Largo Francesco Vito, 1, 00168 Rome, Italy; (A.A.); (D.H.); (C.S.); (A.R.); (M.M.D.G.); (M.D.S.)
- UOC Physics for Life Sciences, Fondazione Policlinico Universitario “A. Gemelli” IRCCS, 00168 Rome, Italy
| | - Michele Maria De Giulio
- Metabolic Intelligence Lab, Department of Neuroscience, Università Cattolica del Sacro Cuore, Largo Francesco Vito, 1, 00168 Rome, Italy; (A.A.); (D.H.); (C.S.); (A.R.); (M.M.D.G.); (M.D.S.)
- UOC Physics for Life Sciences, Fondazione Policlinico Universitario “A. Gemelli” IRCCS, 00168 Rome, Italy
| | - Marco De Spirito
- Metabolic Intelligence Lab, Department of Neuroscience, Università Cattolica del Sacro Cuore, Largo Francesco Vito, 1, 00168 Rome, Italy; (A.A.); (D.H.); (C.S.); (A.R.); (M.M.D.G.); (M.D.S.)
- UOC Physics for Life Sciences, Fondazione Policlinico Universitario “A. Gemelli” IRCCS, 00168 Rome, Italy
| | - Flavio De Maio
- Department of Laboratory and Infectious Sciences, Fondazione Policlinico Universitario A. Gemelli IRCCS, L.go A. Gemelli 8, 00168 Rome, Italy
| | - Giuseppe Maulucci
- Metabolic Intelligence Lab, Department of Neuroscience, Università Cattolica del Sacro Cuore, Largo Francesco Vito, 1, 00168 Rome, Italy; (A.A.); (D.H.); (C.S.); (A.R.); (M.M.D.G.); (M.D.S.)
- UOC Physics for Life Sciences, Fondazione Policlinico Universitario “A. Gemelli” IRCCS, 00168 Rome, Italy
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Lam LK, Tan JT, Ooi PH, Zhang R, Chan KH, Mao X, Hung IFN, Seto WK, Yuen MF, Cheung KS. Effect of metabolic dysfunction-associated steatotic liver disease on BNT162b2 immunogenicity against the severe acute respiratory syndrome coronavirus 2 omicron variant. J Gastroenterol Hepatol 2024; 39:2386-2393. [PMID: 39152762 PMCID: PMC11618226 DOI: 10.1111/jgh.16716] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/29/2024] [Revised: 07/21/2024] [Accepted: 07/30/2024] [Indexed: 08/19/2024]
Abstract
BACKGROUND AND AIM We aimed to investigate the effect of metabolic dysfunction-associated steatotic liver disease (MASLD) on three-dose BNT162b2 immunogenicity to the omicron variant. METHODS Adult recipients of three doses of BNT162b2 were prospectively recruited between May and December 2021. The serology of the neutralizing antibody by live virus microneutralization (vMN) to the omicron variant was measured at baseline, day 180, and day 360 after the first dose. The primary outcome was seroconversion (vMN titer ≥ 10) at day 360. Exposure of interest was MASLD, defined as hepatic steatosis (controlled attenuation parameter ≥ 248 dB/m on transient elastography) plus at least one of five cardiometabolic risk factors. Subjects with prior COVID-19 were excluded. A multivariable logistic regression model was used to derive the adjusted odds ratio of seroconversion with MASLD by adjusting for age, sex, antibiotic use, and proton pump inhibitor use. RESULTS One hundred forty-eight BNT162b2 recipients (male: 48 [32.4%]; median age: 51.0 years [interquartile range, IQR: 44.5-57.3]) were recruited. The median time from the first dose to the third dose was 8.5 months (IQR: 7.9-8.9). MASLD subjects had a lower seroconversion rate than non-MASLD ones (89.6% vs 99.0%; P = 0.007). MASLD was the only independent risk factor for seroconversion (adjusted odds ratio: 0.051, 95% confidence interval: 0.002-0.440). Subgroup analysis of immunogenicity at 4 months after the third dose shows significantly lower vMN titer (13.06 [IQR: 7.69-22.20] vs 33.49 [IQR: 24.05-46.53]; P = 0.004) and seroconversion rate (76.9% vs 97.4%; P = 0.016) in MASLD than non-MASLD subjects, but not within 4 months from the third dose (vMN titer: 46.87 [IQR: 33.12-66.02] vs 41.86 [IQR: 34.47-50.91], P = 0.240; seroconversion rate: 94.3% vs 100%, P = 0.131). CONCLUSION Metabolic dysfunction-associated steatotic liver disease was a risk factor for poorer immunogenicity to the omicron variant, with a more pronounced waning effect compared among three-dose BNT162b2 recipients.
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Affiliation(s)
- Lok Ka Lam
- Department of Medicine, School of Clinical MedicineThe University of Hong Kong, Queen Mary HospitalPok Fu LamHong Kong
| | - Jing Tong Tan
- Department of Medicine, School of Clinical MedicineThe University of Hong Kong, Queen Mary HospitalPok Fu LamHong Kong
| | - Poh Hwa Ooi
- Department of Medicine, School of Clinical MedicineThe University of Hong Kong, Queen Mary HospitalPok Fu LamHong Kong
| | - Ruiqi Zhang
- Department of Medicine, School of Clinical MedicineThe University of Hong Kong, Queen Mary HospitalPok Fu LamHong Kong
| | - Kwok Hung Chan
- Department of MicrobiologyThe University of Hong Kong, Queen Mary HospitalPok Fu LamHong Kong
| | - Xianhua Mao
- Department of Medicine, School of Clinical MedicineThe University of Hong Kong, Queen Mary HospitalPok Fu LamHong Kong
| | - Ivan F N Hung
- Department of Medicine, School of Clinical MedicineThe University of Hong Kong, Queen Mary HospitalPok Fu LamHong Kong
| | - Wai Kay Seto
- Department of Medicine, School of Clinical MedicineThe University of Hong Kong, Queen Mary HospitalPok Fu LamHong Kong
- Department of MedicineThe University of Hong Kong‐Shenzhen HospitalShenzhenChina
- State Key Laboratory of Liver ResearchThe University of Hong KongPok Fu LamHong Kong
| | - Man Fung Yuen
- Department of Medicine, School of Clinical MedicineThe University of Hong Kong, Queen Mary HospitalPok Fu LamHong Kong
- State Key Laboratory of Liver ResearchThe University of Hong KongPok Fu LamHong Kong
| | - Ka Shing Cheung
- Department of Medicine, School of Clinical MedicineThe University of Hong Kong, Queen Mary HospitalPok Fu LamHong Kong
- Department of MedicineThe University of Hong Kong‐Shenzhen HospitalShenzhenChina
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10
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Björmsjö M, Ekström N, Silfverdal SA, Hernell O, Lönnerdal B, Berglund SK. Vaccine response was higher in formula-fed infants compared to breastfed but not affected by lactoferrin or iron in a randomised controlled trial. Acta Paediatr 2024; 113:2266-2274. [PMID: 38934330 DOI: 10.1111/apa.17335] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/25/2023] [Revised: 05/14/2024] [Accepted: 06/14/2024] [Indexed: 06/28/2024]
Abstract
AIM To examine how reduced iron content and added bovine lactoferrin in infant formula affect the antibody response following routine immunisation. METHODS In this randomised controlled trial, 180 Swedish formula-fed infants received, from 6 weeks to 6 months of age, a 2 mg/L iron formula with (n = 72) or without (n = 72) bovine lactoferrin, or a control formula with 8 mg/L iron and no lactoferrin (n = 36). Another 72 infants were recruited as a breastfed reference. Serum immunoglobulin G (IgG) levels against Haemophilus influenzae type b (Hib), diphtheria and tetanus were assessed at four, six and 12 months of age. RESULTS With an equal gender distribution, 180 + 72 term infants were included with a mean age of 7.0 ± 0.7 weeks. At 12 months, infants fed low iron formula showed a significantly higher geometric mean Hib IgG (1.40 μg/mL [1.07-1.83]) compared to the control formula infants (0.67 μg/mL [0.42-1.07]). For all three vaccines, breastfed infants had significantly lower IgG levels at six and 12 months of age. CONCLUSION Except for higher Hib IgG levels at 12 months in infants fed low iron formula, the interventions did not affect vaccine IgG response. Unexpectedly, breastfed infants had significantly lower vaccine IgG levels compared to formula-fed infants.
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Affiliation(s)
- Maria Björmsjö
- Department of Clinical Sciences, Pediatrics, Umeå University, Umeå, Sweden
| | - Nina Ekström
- Department of Health Security, Finnish Institute for Health and Welfare, Helsinki, Finland
| | | | - Olle Hernell
- Department of Clinical Sciences, Pediatrics, Umeå University, Umeå, Sweden
| | - Bo Lönnerdal
- Department of Nutrition, University of California, Davis, California, USA
| | - Staffan K Berglund
- Department of Clinical Sciences, Pediatrics, Umeå University, Umeå, Sweden
- Wallenberg Centre for Molecular Medicine (WCMM), Umeå University, Umeå, Sweden
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11
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Roslund MI, Nurminen N, Oikarinen S, Puhakka R, Grönroos M, Puustinen L, Kummola L, Parajuli A, Cinek O, Laitinen OH, Hyöty H, Sinkkonen A. Skin exposure to soil microbiota elicits changes in cell-mediated immunity to pneumococcal vaccine. Sci Rep 2024; 14:18573. [PMID: 39127736 PMCID: PMC11316737 DOI: 10.1038/s41598-024-68235-8] [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: 09/20/2023] [Accepted: 07/22/2024] [Indexed: 08/12/2024] Open
Abstract
A resilient immune system is characterized by its capacity to respond appropriately to challenges, such as infections, and it is crucial in vaccine response. Here we report a paired randomized intervention-control trial in which we evaluated the effect of microbially rich soil on immune resilience and pneumococcal vaccine response. Twenty-five age and sex matched pairs of volunteers were randomized to intervention and control groups. The intervention group rubbed hands three times a day in microbially rich soil until participants received a pneumococcal vaccine on day 14. Vaccine response, skin and gut bacteriome and blood cytokine levels were analyzed on days 0, 14 and 35. Peripheral blood mononuclear cells (PBMCs) were stimulated with vaccine components and autoclaved soil for cytokine production. Commensal bacterial community shifted only in the intervention group during the 14-day intervention period. When PBMCs collected on day 14 before the vaccination were stimulated with the vaccine components, IFN-y production increased in the intervention but not in the control group. On day 35, vaccination induced a robust antibody response in both groups. In parallel, gut bacterial community was associated with TGF-β plasma levels and TGF-β decrease in plasma was lower in the intervention group. The results indicate that exposure to microbially rich soil can modulate the cell-mediated immunity to components in pneumococcal vaccine.
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Affiliation(s)
- Marja I Roslund
- Natural Resources Institute Finland, Luke, Viikki and Turku, Finland
| | - Noora Nurminen
- Faculty of Medicine and Health Technology, Tampere University, Arvo Ylpön Katu 34, 33520, Tampere, Finland
| | - Sami Oikarinen
- Faculty of Medicine and Health Technology, Tampere University, Arvo Ylpön Katu 34, 33520, Tampere, Finland
| | - Riikka Puhakka
- Ecosystems and Environment Research Programme, Faculty of Biological and Environmental Sciences, University of Helsinki, Niemenkatu 73, 15140, Lahti, Finland
| | - Mira Grönroos
- Ecosystems and Environment Research Programme, Faculty of Biological and Environmental Sciences, University of Helsinki, Niemenkatu 73, 15140, Lahti, Finland
| | - Leena Puustinen
- Faculty of Medicine and Health Technology, Tampere University, Arvo Ylpön Katu 34, 33520, Tampere, Finland
| | - Laura Kummola
- Faculty of Medicine and Health Technology, Tampere University, Arvo Ylpön Katu 34, 33520, Tampere, Finland
| | - Anirudra Parajuli
- Ecosystems and Environment Research Programme, Faculty of Biological and Environmental Sciences, University of Helsinki, Niemenkatu 73, 15140, Lahti, Finland
- Department of Medicine, Karolinska Institutet, Huddinge, Sweden
| | - Ondřej Cinek
- Department of Medical Microbiology, 2nd Faculty of Medicine, Charles University, V Úvalu 84, Praha 5, 150 06, Prague, Czech Republic
| | - Olli H Laitinen
- Faculty of Medicine and Health Technology, Tampere University, Arvo Ylpön Katu 34, 33520, Tampere, Finland
| | - Heikki Hyöty
- Faculty of Medicine and Health Technology, Tampere University, Arvo Ylpön Katu 34, 33520, Tampere, Finland
- Fimlab Laboratories, Pirkanmaa Hospital District, Tampere, Finland
| | - Aki Sinkkonen
- Natural Resources Institute Finland, Luke, Viikki and Turku, Finland.
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12
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Zhong K, Chen X, Zhang J, Jiang X, Zhang J, Huang M, Bi S, Ju C, Luo Y. Recent Advances in Oral Vaccines for Animals. Vet Sci 2024; 11:353. [PMID: 39195807 PMCID: PMC11360704 DOI: 10.3390/vetsci11080353] [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: 07/01/2024] [Revised: 07/29/2024] [Accepted: 08/02/2024] [Indexed: 08/29/2024] Open
Abstract
Compared to traditional injected vaccines, oral vaccines offer significant advantages for the immunization of livestock and wildlife due to their ease of use, high compliance, improved safety, and potential to stimulate mucosal immune responses and induce systemic immunity against pathogens. This review provides an overview of the delivery methods for oral vaccines, and the factors that influence their immunogenicity. We also highlight the global progress and achievements in the development and use of oral vaccines for animals, shedding light on potential future applications in this field.
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Affiliation(s)
- Kaining Zhong
- College of Veterinary Medicine, South China Agricultural University, Guangzhou 510640, China; (K.Z.); (X.C.); (J.Z.); (X.J.); (J.Z.); (M.H.)
| | - Xinting Chen
- College of Veterinary Medicine, South China Agricultural University, Guangzhou 510640, China; (K.Z.); (X.C.); (J.Z.); (X.J.); (J.Z.); (M.H.)
| | - Junhao Zhang
- College of Veterinary Medicine, South China Agricultural University, Guangzhou 510640, China; (K.Z.); (X.C.); (J.Z.); (X.J.); (J.Z.); (M.H.)
| | - Xiaoyu Jiang
- College of Veterinary Medicine, South China Agricultural University, Guangzhou 510640, China; (K.Z.); (X.C.); (J.Z.); (X.J.); (J.Z.); (M.H.)
| | - Junhui Zhang
- College of Veterinary Medicine, South China Agricultural University, Guangzhou 510640, China; (K.Z.); (X.C.); (J.Z.); (X.J.); (J.Z.); (M.H.)
| | - Minyi Huang
- College of Veterinary Medicine, South China Agricultural University, Guangzhou 510640, China; (K.Z.); (X.C.); (J.Z.); (X.J.); (J.Z.); (M.H.)
| | - Shuilian Bi
- School of Food Science, Guangdong Pharmaceutical University, Zhongshan 528458, China;
| | - Chunmei Ju
- College of Veterinary Medicine, South China Agricultural University, Guangzhou 510640, China; (K.Z.); (X.C.); (J.Z.); (X.J.); (J.Z.); (M.H.)
- Key Laboratory of Animal Vaccine Development of the Ministry of Agriculture and Rural Affairs, South China Agricultural University, Guangzhou 510640, China
| | - Yongwen Luo
- College of Veterinary Medicine, South China Agricultural University, Guangzhou 510640, China; (K.Z.); (X.C.); (J.Z.); (X.J.); (J.Z.); (M.H.)
- Key Laboratory of Animal Vaccine Development of the Ministry of Agriculture and Rural Affairs, South China Agricultural University, Guangzhou 510640, China
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13
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Liu Y, Zhou J, Yang Y, Chen X, Chen L, Wu Y. Intestinal Microbiota and Its Effect on Vaccine-Induced Immune Amplification and Tolerance. Vaccines (Basel) 2024; 12:868. [PMID: 39203994 PMCID: PMC11359036 DOI: 10.3390/vaccines12080868] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2024] [Revised: 07/22/2024] [Accepted: 07/24/2024] [Indexed: 09/03/2024] Open
Abstract
This review provides the potential of intestinal microbiota in vaccine design and application, exploring the current insights into the interplay between the intestinal microbiota and the immune system, with a focus on its intermediary function in vaccine efficacy. It summarizes families and genera of bacteria that are part of the intestinal microbiota that may enhance or diminish vaccine efficacy and discusses the foundational principles of vaccine sequence design and the application of gut microbial characteristics in vaccine development. Future research should further investigate the use of multi-omics technologies to elucidate the interactive mechanisms between intestinal microbiota and vaccine-induced immune responses, aiming to optimize and improve vaccine design.
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Affiliation(s)
- Yixin Liu
- Department of Pulmonary and Critical Care Medicine, West China Hospital, Sichuan University, Chengdu 610041, China;
- Department of Thoracic Surgery, West China Hospital, Sichuan University, Chengdu 610041, China; (J.Z.); (L.C.)
| | - Jianfeng Zhou
- Department of Thoracic Surgery, West China Hospital, Sichuan University, Chengdu 610041, China; (J.Z.); (L.C.)
| | - Yushang Yang
- Department of Thoracic Surgery, West China Hospital, Sichuan University, Chengdu 610041, China; (J.Z.); (L.C.)
| | - Xiangzheng Chen
- Department of Liver Surgery & Liver Transplantation, West China Hospital, Sichuan University, Chengdu 610041, China;
| | - Longqi Chen
- Department of Thoracic Surgery, West China Hospital, Sichuan University, Chengdu 610041, China; (J.Z.); (L.C.)
| | - Yangping Wu
- Department of Pulmonary and Critical Care Medicine, West China Hospital, Sichuan University, Chengdu 610041, China;
- State Key Laboratory of Respiratory Health and Multimorbidity, West China Hospital, Chengdu 610041, China
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14
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Larbi A. From Genesis to Old Age: Exploring the Immune System One Cell at a Time with Flow Cytometry. Biomedicines 2024; 12:1469. [PMID: 39062042 PMCID: PMC11275137 DOI: 10.3390/biomedicines12071469] [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: 05/12/2024] [Revised: 06/21/2024] [Accepted: 06/28/2024] [Indexed: 07/28/2024] Open
Abstract
The immune system is a highly complex and tightly regulated system that plays a crucial role in protecting the body against external threats, such as pathogens, and internal abnormalities, like cancer cells. It undergoes development during fetal stages and continuously learns from each encounter with pathogens, allowing it to develop immunological memory and provide a wide range of immune protection. Over time, after numerous encounters and years of functioning, the immune system can begin to show signs of erosion, which is commonly named immunosenescence. In this review, we aim to explore how the immune system responds to initial encounters with antigens and how it handles persistent stimulations throughout a person's lifetime. Our understanding of the immune system has greatly benefited from advanced technologies like flow cytometry. In this context, we will discuss the valuable contribution of flow cytometry in enhancing our knowledge of the immune system behavior in aging, with a specific focus on T-cells. Moreover, we will expand our discussion to the flow cytometry-based assessment of extracellular vesicles, a recently discovered communication channel in biology, and their implications for immune system functioning.
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Affiliation(s)
- Anis Larbi
- Medical and Scientific Affairs, Beckman Coulter Life Sciences, 22 Avenue des Nations, 93420 Villepinte, France;
- Department of Medicine, Division of Geriatrics, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, QC J1K 2R1, Canada
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15
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Song J, Zhang Y, Zhou C, Zhan J, Cheng X, Huang H, Mao S, Zong Z. The dawn of a new Era: mRNA vaccines in colorectal cancer immunotherapy. Int Immunopharmacol 2024; 132:112037. [PMID: 38599100 DOI: 10.1016/j.intimp.2024.112037] [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: 02/06/2024] [Revised: 03/24/2024] [Accepted: 04/05/2024] [Indexed: 04/12/2024]
Abstract
Colorectal cancer (CRC) is a typical cancer that accounts for 10% of all new cancer cases annually and nearly 10% of all cancer deaths. Despite significant progress in current classical interventions for CRC, these traditional strategies could be invasive and with numerous adverse effects. The poor prognosis of CRC patients highlights the evident and pressing need for more efficient and targeted treatment. Novel strategies regarding mRNA vaccines for anti-tumor therapy have also been well-developed since the successful application for the prevention of COVID-19. mRNA vaccine technology won the 2023 Nobel Prize in Physiology or Medicine, signaling a new direction in human anti-cancer treatment: mRNA medicine. As a promising new immunotherapy in CRC and other multiple cancer treatments, the mRNA vaccine has higher specificity, better efficacy, and fewer side effects than traditional strategies. The present review outlines the basics of mRNA vaccines and their advantages over other vaccines and informs an available strategy for developing efficient mRNA vaccines for CRC precise treatment. In the future, more exploration of mRNA vaccines for CRC shall be attached, fostering innovation to address existing limitations.
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Affiliation(s)
- Jingjing Song
- Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Nanchang University, No.1 MinDe Road, Nanchang 330006, Jiangxi, China; School of Ophthalmology and Optometry, Nanchang University, Nanchang 330006, Jiangxi, China
| | - Yujun Zhang
- Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Nanchang University, No.1 MinDe Road, Nanchang 330006, Jiangxi, China; Huankui Academy, Nanchang University, Nanchang 330006, Jiangxi, China
| | - Chulin Zhou
- Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Nanchang University, No.1 MinDe Road, Nanchang 330006, Jiangxi, China; The Second Clinical Medical College, Nanchang University, Nanchang 330006, Jiangxi, China
| | - Jianhao Zhan
- Huankui Academy, Nanchang University, Nanchang 330006, Jiangxi, China
| | - Xifu Cheng
- School of Ophthalmology and Optometry, Nanchang University, Nanchang 330006, Jiangxi, China
| | - Haoyu Huang
- Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Nanchang University, No.1 MinDe Road, Nanchang 330006, Jiangxi, China
| | - Shengxun Mao
- Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Nanchang University, No.1 MinDe Road, Nanchang 330006, Jiangxi, China.
| | - Zhen Zong
- Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Nanchang University, No.1 MinDe Road, Nanchang 330006, Jiangxi, China.
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16
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Lecoeur A, Blanc F, Gourichon D, Bruneau N, Burlot T, Pinard-van der Laan MH, Calenge F. Host genetics drives differences in cecal microbiota composition and immune traits of laying hens raised in the same environment. Poult Sci 2024; 103:103609. [PMID: 38547541 PMCID: PMC11000118 DOI: 10.1016/j.psj.2024.103609] [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: 12/14/2023] [Revised: 02/12/2024] [Accepted: 02/28/2024] [Indexed: 04/11/2024] Open
Abstract
Vaccination is one of the most effective strategies for preventing infectious diseases but individual vaccine responses are highly heterogeneous. Host genetics and gut microbiota composition are 2 likely drivers of this heterogeneity. We studied 94 animals belonging to 4 lines of laying hens: a White Leghorn experimental line genetically selected for a high antibody response against the Newcastle Disease Virus (NDV) vaccine (ND3) and its unselected control line (CTR), and 2 commercial lines (White Leghorn [LEG] and Rhode Island Red [RIR]). Animals were reared in the same conditions from hatching to 42 d of age, and animals from different genetic lines were mixed. Animals were vaccinated at 22 d of age and their humoral vaccine response against NDV was assessed by hemagglutination inhibition assay and ELISA from blood samples collected at 15, 19, and 21 d after vaccination. The immune parameters studied were the 3 immunoglobulins subtypes A, M, and Y and the blood cell composition was assessed by flow cytometry. The composition of the cecal microbiota was assessed at the end of the experiment by analyzing amplified 16S rRNA gene sequences to obtain amplicon sequence variants (ASV). The 4 lines showed significantly different levels of NDV vaccine response at the 3 measured points, with, logically, a higher response of the genetically selected ND3 line, and intermediate and low responses for the unselected CTR control line and for the 2 commercial lines, respectively. The ND3 line displayed also a higher proportion of immunoglobulins (IgA, IgM, and IgY). The RIR line showed the most different blood cell composition. The 4 lines showed significantly different microbiota characteristics: composition, abundances at all taxonomic levels, and correlations between genera and vaccine response. The tested genetic lines differ for immune parameters and gut microbiota composition and functions. These phenotypic differences can be attributed to genetic differences between lines. Causal relationships between both types of parameters are discussed and will be investigated in further studies.
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Affiliation(s)
- Alexandre Lecoeur
- Université Paris-Saclay, INRAE, AgroParisTech, Jouy-en-Josas 78350, France.
| | - Fany Blanc
- Université Paris-Saclay, INRAE, AgroParisTech, Jouy-en-Josas 78350, France
| | | | - Nicolas Bruneau
- Université Paris-Saclay, INRAE, AgroParisTech, Jouy-en-Josas 78350, France
| | | | | | - Fanny Calenge
- Université Paris-Saclay, INRAE, AgroParisTech, Jouy-en-Josas 78350, France
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17
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Chen G, Han Q, Li WX, Hai R, Ding SW. Live-attenuated virus vaccine defective in RNAi suppression induces rapid protection in neonatal and adult mice lacking mature B and T cells. Proc Natl Acad Sci U S A 2024; 121:e2321170121. [PMID: 38630724 PMCID: PMC11046691 DOI: 10.1073/pnas.2321170121] [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: 12/01/2023] [Accepted: 03/15/2024] [Indexed: 04/19/2024] Open
Abstract
Global control of infectious diseases depends on the continuous development and deployment of diverse vaccination strategies. Currently available live-attenuated and killed virus vaccines typically take a week or longer to activate specific protection by the adaptive immunity. The mosquito-transmitted Nodamura virus (NoV) is attenuated in mice by mutations that prevent expression of the B2 viral suppressor of RNA interference (VSR) and consequently, drastically enhance in vivo production of the virus-targeting small-interfering RNAs. We reported recently that 2 d after immunization with live-attenuated VSR-disabled NoV (NoVΔB2), neonatal mice become fully protected against lethal NoV challenge and develop no detectable infection. Using Rag1-/- mice that produce no mature B and T lymphocytes as a model, here we examined the hypothesis that adaptive immunity is dispensable for the RNAi-based protective immunity activated by NoVΔB2 immunization. We show that immunization of both neonatal and adult Rag1-/- mice with live but not killed NoVΔB2 induces full protection against NoV challenge at 2 or 14 d postimmunization. Moreover, NoVΔB2-induced protective antiviral immunity is virus-specific and remains effective in adult Rag1-/- mice 42 and 90 d after a single-shot immunization. We conclude that immunization with the live-attenuated VSR-disabled RNA virus vaccine activates rapid and long-lasting protective immunity against lethal challenges by a distinct mechanism independent of the adaptive immunity mediated by B and T cells. Future studies are warranted to determine whether additional animal and human viruses attenuated by VSR inactivation induce similar protective immunity in healthy and adaptive immunity-compromised individuals.
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Affiliation(s)
- Gang Chen
- Department of Microbiology and Plant Pathology, University of California, Riverside, CA92521
| | - Qingxia Han
- Department of Microbiology and Plant Pathology, University of California, Riverside, CA92521
| | - Wan-Xiang Li
- Department of Microbiology and Plant Pathology, University of California, Riverside, CA92521
| | - Rong Hai
- Department of Microbiology and Plant Pathology, University of California, Riverside, CA92521
| | - Shou-Wei Ding
- Department of Microbiology and Plant Pathology, University of California, Riverside, CA92521
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18
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McCumber AW, Kim YJ, Granek J, Tighe RM, Gunsch CK. Soil exposure modulates the immune response to an influenza challenge in a mouse model. THE SCIENCE OF THE TOTAL ENVIRONMENT 2024; 922:170865. [PMID: 38340827 DOI: 10.1016/j.scitotenv.2024.170865] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/25/2023] [Revised: 02/06/2024] [Accepted: 02/07/2024] [Indexed: 02/12/2024]
Abstract
There is increasing evidence that early life microbial exposure aids in immune system maturation, more recently known as the "old friends" hypothesis. To test this hypothesis, 4-week-old mice were exposed to soils of increasing microbial diversity for four weeks followed by an intranasal challenge with either live or heat inactivated influenza A virus and monitored for 7 additional days. Perturbations of the gut and lung microbiomes were explored through 16S rRNA amplicon sequencing. RNA-sequencing was used to examine the host response in the lung tissue through differential gene expression. We determined that compared to the gut microbiome, the lung microbiome is more susceptible to changes in beta diversity following soil exposure with Lachnospiraceae ASVs accounting for most of the differences between groups. While several immune system genes were found to be significantly differentially expressed in lung tissue due to soil exposures, there were no differences in viral load or weight loss. This study shows that exposure to diverse microbial communities through soil exposure alters the gut and lung microbiomes resulting in differential expression of specific immune system related genes within the lung following an influenza challenge.
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Affiliation(s)
- Alexander W McCumber
- Department of Environmental Sciences and Engineering, University of North Carolina, Chapel Hill, Chapel Hill, NC, USA
| | - Yeon Ji Kim
- Civil and Environmental Engineering Department, Duke University, Durham, NC, USA
| | - Joshua Granek
- Department of Biostatistics and Bioinformatics, Duke University, Durham, NC, USA
| | - Robert M Tighe
- Department of Medicine, Duke University, Durham, NC, USA
| | - Claudia K Gunsch
- Civil and Environmental Engineering Department, Duke University, Durham, NC, USA.
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19
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Nolin SJ, Siegel PB, Ashwell CM. Differences in the microbiome of the small intestine of Leghorn lines divergently selected for antibody titer to sheep erythrocytes suggest roles for commensals in host humoral response. Front Physiol 2024; 14:1304051. [PMID: 38260103 PMCID: PMC10800846 DOI: 10.3389/fphys.2023.1304051] [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: 09/28/2023] [Accepted: 12/18/2023] [Indexed: 01/24/2024] Open
Abstract
For forty generations, two lines of White Leghorn chickens have been selected for high (HAS) or low (LAS) antibody response to a low dose injection of sheep red blood cells (SRBCs). Their gut is home to billons of microorganisms and the largest number of immune cells in the body; therefore, the objective of this experiment was to gain understanding of the ways the microbiome may influence the differential antibody response observed in these lines. We achieved this by characterizing the small intestinal microbiome of HAS and LAS chickens, determining their functional microbiome profiles, and by using machine learning to identify microbes which best differentiate HAS from LAS and associating the abundance of those microbes with host gene expression. Microbiome sequencing revealed greater diversity in LAS but statistically higher abundance of several strains, particularly those of Lactobacillus, in HAS. Enrichment of microbial metabolites implicated in immune response such as lactic acid, short chain fatty acids, amino acids, and vitamins were different between HAS and LAS. The abundance of several microbial strains corresponds to enriched host gene expression pathways related to immune response. These data provide a compelling argument that the microbiome is both likely affected by host divergent genetic selection and that it exerts influence on host antibody response by various mechanisms.
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Affiliation(s)
- Shelly J. Nolin
- Prestage Department of Poultry Science, North Carolina State University, Raleigh, NC, United States
| | - Paul B. Siegel
- School of Animal Science, Virginia Polytechnic Institute and State University, Blacksburg, VA, United States
| | - Christopher M. Ashwell
- Davis College of Agriculture, Natural Resources, and Design, West Virginia University, Morgantown, WV, United States
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20
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Potchen NB, Johnson AM, Hager K, Graham J, Van P, Lyn-Kew KH, Warrier L, Talavera IC, Lund JM, Kublin JG. Oral tolerance to systemic vaccination remains intact without RORγt expression in regulatory T cells. iScience 2023; 26:108504. [PMID: 38125026 PMCID: PMC10730369 DOI: 10.1016/j.isci.2023.108504] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2023] [Revised: 09/29/2023] [Accepted: 11/17/2023] [Indexed: 12/23/2023] Open
Abstract
Many promising vaccine candidates and licensed vaccines lead to variable immune responses within humans. Studies suggest that environmental exposures in the gastrointestinal tract could contribute to a reduction in vaccine efficacy via immune tolerance at this site; this is partly achieved by a high abundance of regulatory T cells (Tregs). It is unclear if Treg subsets regulate systemic vaccine responses following oral antigen pre-exposure. Here, we implemented a conditional knock-out mouse model of RORγt+ Tregs to examine the role of these cells in mediating this process. Following oral exposure to the model antigen ovalbumin (OVA) prior to immunization, we found similar induction of vaccine-induced antibody responses in mice lacking RORγt expression in Tregs compared to sufficient controls. Use of various adjuvants led to distinct findings. Our data suggest that expression of RORγt+ within Tregs is not required to regulate tolerance to systemic vaccination following oral antigen exposure.
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Affiliation(s)
- Nicole B. Potchen
- Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA 98109, USA
- Department of Global Health, University of Washington, Seattle, WA 98195, USA
| | - Andrew M.F. Johnson
- Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA 98109, USA
| | - Kevin Hager
- Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA 98109, USA
| | - Jessica Graham
- Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA 98109, USA
| | - Phuong Van
- Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA 98109, USA
| | - Katelyn H. Lyn-Kew
- Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA 98109, USA
| | - Lakshmi Warrier
- Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA 98109, USA
- Department of Global Health, University of Washington, Seattle, WA 98195, USA
| | - Irene Cruz Talavera
- Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA 98109, USA
- Department of Global Health, University of Washington, Seattle, WA 98195, USA
| | - Jennifer M. Lund
- Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA 98109, USA
- Department of Global Health, University of Washington, Seattle, WA 98195, USA
| | - James G. Kublin
- Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA 98109, USA
- Department of Global Health, University of Washington, Seattle, WA 98195, USA
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21
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Saito H, Yoshimura H, Yoshida M, Tani Y, Kawashima M, Uchiyama T, Zhao T, Yamamoto C, Kobashi Y, Sawano T, Imoto S, Park H, Nakamura N, Iwami S, Kaneko Y, Nakayama A, Kodama T, Wakui M, Kawamura T, Tsubokura M. Antibody Profiling of Microbial Antigens in the Blood of COVID-19 mRNA Vaccine Recipients Using Microbial Protein Microarrays. Vaccines (Basel) 2023; 11:1694. [PMID: 38006026 PMCID: PMC10674746 DOI: 10.3390/vaccines11111694] [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: 09/07/2023] [Revised: 10/26/2023] [Accepted: 11/04/2023] [Indexed: 11/26/2023] Open
Abstract
Although studies have demonstrated that infections with various viruses, bacteria, and parasites can modulate the immune system, no study has investigated changes in antibodies against microbial antigens after the COVID-19 mRNA vaccination. IgG antibodies against microbial antigens in the blood of vaccinees were comprehensively analyzed using microbial protein microarrays that carried approximately 5000 microbe-derived proteins. Changes in antibodies against microbial antigens were scrutinized in healthy participants enrolled in the Fukushima Vaccination Community Survey conducted in Fukushima Prefecture, Japan, after their second and third COVID-19 mRNA vaccinations. Antibody profiling of six groups stratified by antibody titer and the remaining neutralizing antibodies was also performed to study the dynamics of neutralizing antibodies against SARS-CoV-2 and the changes in antibodies against microbial antigens. The results showed that changes in antibodies against microbial antigens other than SARS-CoV-2 antigens were extremely limited after COVID-19 vaccination. In addition, antibodies against a staphylococcal complement inhibitor have been identified as microbial antigens that are associated with increased levels of neutralizing antibodies against SARS-CoV-2. These antibodies may be a predictor of the maintenance of neutralizing antibodies following the administration of a COVID-19 mRNA vaccine.
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Affiliation(s)
- Hiroaki Saito
- Department of Radiation Health Management, Fukushima Medical University School of Medicine, Fukushima, Fukushima 960-1247, Japan
- Department of Internal Medicine, Soma Central Hospital, Soma, Fukushima 976-0016, Japan
| | - Hiroki Yoshimura
- Department of Radiation Health Management, Fukushima Medical University School of Medicine, Fukushima, Fukushima 960-1247, Japan
- School of Medicine, Hiroshima University, Hiroshima, Hiroshima 739-8511, Japan
| | - Makoto Yoshida
- Department of Radiation Health Management, Fukushima Medical University School of Medicine, Fukushima, Fukushima 960-1247, Japan
- Faculty of Medicine, Teikyo University School of Medicine, Itabashi-ku, Tokyo 173-8605, Japan
| | - Yuta Tani
- Medical Governance Research Institute, Minato-ku, Tokyo 108-0074, Japan
- Department of Laboratory Medicine, Keio University School of Medicine, Shinjuku-ku, Tokyo 160-8582, Japan
| | - Moe Kawashima
- Department of Radiation Health Management, Fukushima Medical University School of Medicine, Fukushima, Fukushima 960-1247, Japan
| | - Taiga Uchiyama
- Department of Radiation Health Management, Fukushima Medical University School of Medicine, Fukushima, Fukushima 960-1247, Japan
| | - Tianchen Zhao
- Department of Radiation Health Management, Fukushima Medical University School of Medicine, Fukushima, Fukushima 960-1247, Japan
| | - Chika Yamamoto
- Department of Radiation Health Management, Fukushima Medical University School of Medicine, Fukushima, Fukushima 960-1247, Japan
| | - Yurie Kobashi
- Department of Radiation Health Management, Fukushima Medical University School of Medicine, Fukushima, Fukushima 960-1247, Japan
- Department of Internal Medicine, Serireikai Group Hirata Central Hospital, Ishikawa County, Fukushima 963-8202, Japan
| | - Toyoaki Sawano
- Department of Radiation Health Management, Fukushima Medical University School of Medicine, Fukushima, Fukushima 960-1247, Japan
| | - Seiya Imoto
- Division of Health Medical Intelligence, Human Genome Center, Institute of Medical Science, The University of Tokyo, Shirokanedai, Minato-ku, Tokyo 108-8639, Japan
| | - Hyeongki Park
- Interdisciplinary Biology Laboratory (iBLab), Division of Natural Science, Graduate School of Science, Nagoya University, Chikusa-ku, Nagoya 464-8601, Japan (S.I.)
| | - Naotoshi Nakamura
- Interdisciplinary Biology Laboratory (iBLab), Division of Natural Science, Graduate School of Science, Nagoya University, Chikusa-ku, Nagoya 464-8601, Japan (S.I.)
| | - Shingo Iwami
- Interdisciplinary Biology Laboratory (iBLab), Division of Natural Science, Graduate School of Science, Nagoya University, Chikusa-ku, Nagoya 464-8601, Japan (S.I.)
| | - Yudai Kaneko
- Medical & Biological Laboratories Co., Ltd., Minato-ku, Tokyo 105-0012, Japan
- Laboratory for Systems Biology and Medicine, Research Centre for Advanced Science and Technology (RCAST), The University of Tokyo, Meguro-ku, Tokyo 153-8904, Japan
| | - Aya Nakayama
- Isotope Science Centre, The University of Tokyo, Bunkyo-ku, Tokyo 113-0032, Japan
| | - Tatsuhiko Kodama
- Laboratory for Systems Biology and Medicine, Research Centre for Advanced Science and Technology (RCAST), The University of Tokyo, Meguro-ku, Tokyo 153-8904, Japan
| | - Masatoshi Wakui
- Department of Laboratory Medicine, Keio University School of Medicine, Shinjuku-ku, Tokyo 160-8582, Japan
| | - Takeshi Kawamura
- Laboratory for Systems Biology and Medicine, Research Centre for Advanced Science and Technology (RCAST), The University of Tokyo, Meguro-ku, Tokyo 153-8904, Japan
- Isotope Science Centre, The University of Tokyo, Bunkyo-ku, Tokyo 113-0032, Japan
| | - Masaharu Tsubokura
- Department of Radiation Health Management, Fukushima Medical University School of Medicine, Fukushima, Fukushima 960-1247, Japan
- Department of Internal Medicine, Soma Central Hospital, Soma, Fukushima 976-0016, Japan
- Department of Internal Medicine, Serireikai Group Hirata Central Hospital, Ishikawa County, Fukushima 963-8202, Japan
- Minamisoma Municipal General Hospital, Minamisoma, Fukushima 975-0033, Japan
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22
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Nehar-Belaid D, Sokolowski M, Ravichandran S, Banchereau J, Chaussabel D, Ucar D. Baseline immune states (BIS) associated with vaccine responsiveness and factors that shape the BIS. Semin Immunol 2023; 70:101842. [PMID: 37717525 DOI: 10.1016/j.smim.2023.101842] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/30/2023] [Accepted: 09/11/2023] [Indexed: 09/19/2023]
Abstract
Vaccines are among the greatest inventions in medicine, leading to the elimination or control of numerous diseases, including smallpox, polio, measles, rubella, and, most recently, COVID-19. Yet, the effectiveness of vaccines varies among individuals. In fact, while some recipients mount a robust response to vaccination that protects them from the disease, others fail to respond. Multiple clinical and epidemiological factors contribute to this heterogeneity in responsiveness. Systems immunology studies fueled by advances in single-cell biology have been instrumental in uncovering pre-vaccination immune cell types and genomic features (i.e., the baseline immune state, BIS) that have been associated with vaccine responsiveness. Here, we review clinical factors that shape the BIS, and the characteristics of the BIS associated with responsiveness to frequently studied vaccines (i.e., influenza, COVID-19, bacterial pneumonia, malaria). Finally, we discuss potential strategies to enhance vaccine responsiveness in high-risk groups, focusing specifically on older adults.
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Affiliation(s)
| | - Mark Sokolowski
- The Jackson Laboratory for Genomic Medicine, Farmington, CT 06030, USA
| | | | | | - Damien Chaussabel
- The Jackson Laboratory for Genomic Medicine, Farmington, CT 06030, USA
| | - Duygu Ucar
- The Jackson Laboratory for Genomic Medicine, Farmington, CT 06030, USA; Institute for Systems Genomics, University of Connecticut Health Center, Farmington, CT, USA.
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23
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Shaffer M, Best K, Tang C, Liang X, Schulz S, Gonzalez E, White CH, Wyche TP, Kang J, Wesseling H, Topçuoğlu BD, Cairns T, Sana TR, Kaufhold RM, Maritz JM, Woelk CH, Swaminathan G, Norton JE, Pichichero ME. Very early life microbiome and metabolome correlates with primary vaccination variability in children. mSystems 2023; 8:e0066123. [PMID: 37610205 PMCID: PMC10654091 DOI: 10.1128/msystems.00661-23] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2023] [Accepted: 07/12/2023] [Indexed: 08/24/2023] Open
Abstract
IMPORTANCE We show that simultaneous study of stool and nasopharyngeal microbiome reveals divergent timing and patterns of maturation, suggesting that local mucosal factors may influence microbiome composition in the gut and respiratory system. Antibiotic exposure in early life as occurs commonly, may have an adverse effect on vaccine responsiveness. Abundance of gut and/or nasopharyngeal bacteria with the machinery to produce lipopolysaccharide-a toll-like receptor 4 agonist-may positively affect future vaccine protection, potentially by acting as a natural adjuvant. The increased levels of serum phenylpyruvic acid in infants with lower vaccine-induced antibody levels suggest an increased abundance of hydrogen peroxide, leading to more oxidative stress in low vaccine-responding infants.
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Affiliation(s)
- Michael Shaffer
- Exploratory Science Center, Merck & Co., Inc., Cambridge, Massachusetts, USA
| | - Katharine Best
- Exploratory Science Center, Merck & Co., Inc., Cambridge, Massachusetts, USA
| | - Catherine Tang
- Exploratory Science Center, Merck & Co., Inc., Cambridge, Massachusetts, USA
| | - Xue Liang
- Exploratory Science Center, Merck & Co., Inc., Cambridge, Massachusetts, USA
| | - Steven Schulz
- Rochester General Hospital Research Institute, Center for Infectious Diseases and Immunology, Rochester, New York, USA
| | - Eduardo Gonzalez
- Rochester General Hospital Research Institute, Center for Infectious Diseases and Immunology, Rochester, New York, USA
| | - Cory H. White
- Exploratory Science Center, Merck & Co., Inc., Cambridge, Massachusetts, USA
| | - Thomas P. Wyche
- Exploratory Science Center, Merck & Co., Inc., Cambridge, Massachusetts, USA
| | - John Kang
- Exploratory Science Center, Merck & Co., Inc., Cambridge, Massachusetts, USA
| | - Hendrik Wesseling
- Exploratory Science Center, Merck & Co., Inc., Cambridge, Massachusetts, USA
| | - Begüm D. Topçuoğlu
- Exploratory Science Center, Merck & Co., Inc., Cambridge, Massachusetts, USA
| | - Thomas Cairns
- Exploratory Science Center, Merck & Co., Inc., Cambridge, Massachusetts, USA
| | - Theodore R. Sana
- Exploratory Science Center, Merck & Co., Inc., Cambridge, Massachusetts, USA
| | - Robin M. Kaufhold
- Infectious Diseases and Vaccine Research, MRL, Merck & Co., Inc., West Point, Pennsylvania, USA
| | - Julia M. Maritz
- Exploratory Science Center, Merck & Co., Inc., Cambridge, Massachusetts, USA
| | | | - Gokul Swaminathan
- Exploratory Science Center, Merck & Co., Inc., Cambridge, Massachusetts, USA
| | - James E. Norton
- Exploratory Science Center, Merck & Co., Inc., Cambridge, Massachusetts, USA
| | - Michael E. Pichichero
- Rochester General Hospital Research Institute, Center for Infectious Diseases and Immunology, Rochester, New York, USA
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24
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Dotiwala F, Upadhyay AK. Next Generation Mucosal Vaccine Strategy for Respiratory Pathogens. Vaccines (Basel) 2023; 11:1585. [PMID: 37896988 PMCID: PMC10611113 DOI: 10.3390/vaccines11101585] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2023] [Revised: 10/06/2023] [Accepted: 10/10/2023] [Indexed: 10/29/2023] Open
Abstract
Inducing humoral and cytotoxic mucosal immunity at the sites of pathogen entry has the potential to prevent the infection from getting established. This is different from systemic vaccination, which protects against the development of systemic symptoms. The field of mucosal vaccination has seen fewer technological advances compared to nucleic acid and subunit vaccine advances for injectable vaccine platforms. The advent of the next-generation adenoviral vectors has given a boost to mucosal vaccine research. Basic research into the mechanisms regulating innate and adaptive mucosal immunity and the discovery of effective and safe mucosal vaccine adjuvants will continue to improve mucosal vaccine design. The results from clinical trials of inhaled COVID-19 vaccines demonstrate their ability to induce the proliferation of cytotoxic T cells and the production of secreted IgA and IgG antibodies locally, unlike intramuscular vaccinations. However, these mucosal vaccines induce systemic immune responses at par with systemic vaccinations. This review summarizes the function of the respiratory mucosa-associated lymphoid tissue and the advantages that the adenoviral vectors provide as inhaled vaccine platforms.
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Affiliation(s)
- Farokh Dotiwala
- Ocugen Inc., 11 Great Valley Parkway, Malvern, PA 19355, USA
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25
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Wang J, Zhao Y, Nie G. Intelligent nanomaterials for cancer therapy: recent progresses and future possibilities. MEDICAL REVIEW (2021) 2023; 3:321-342. [PMID: 38235406 PMCID: PMC10790212 DOI: 10.1515/mr-2023-0028] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/07/2023] [Accepted: 08/15/2023] [Indexed: 01/19/2024]
Abstract
Intelligent nanomedicine is currently one of the most active frontiers in cancer therapy development. Empowered by the recent progresses of nanobiotechnology, a new generation of multifunctional nanotherapeutics and imaging platforms has remarkably improved our capability to cope with the highly heterogeneous and complicated nature of cancer. With rationally designed multifunctionality and programmable assembly of functional subunits, the in vivo behaviors of intelligent nanosystems have become increasingly tunable, making them more efficient in performing sophisticated actions in physiological and pathological microenvironments. In recent years, intelligent nanomaterial-based theranostic platforms have showed great potential in tumor-targeted delivery, biological barrier circumvention, multi-responsive tumor sensing and drug release, as well as convergence with precise medication approaches such as personalized tumor vaccines. On the other hand, the increasing system complexity of anti-cancer nanomedicines also pose significant challenges in characterization, monitoring and clinical use, requesting a more comprehensive and dynamic understanding of nano-bio interactions. This review aims to briefly summarize the recent progresses achieved by intelligent nanomaterials in tumor-targeted drug delivery, tumor immunotherapy and temporospatially specific tumor imaging, as well as important advances of our knowledge on their interaction with biological systems. In the perspective of clinical translation, we have further discussed the major possibilities provided by disease-oriented development of anti-cancer nanomaterials, highlighting the critical importance clinically-oriented system design.
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Affiliation(s)
- Jing Wang
- CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, CAS Center of Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing, China
- Center of Materials Science and Optoelectronics Engineering, University of Chinese Academy of Sciences, Beijing, China
| | - Yuliang Zhao
- CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, CAS Center of Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing, China
- GBA Research Innovation Institute for Nanotechnology, Guangzhou, Guangdong Province, China
| | - Guangjun Nie
- CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, CAS Center of Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing, China
- Center of Materials Science and Optoelectronics Engineering, University of Chinese Academy of Sciences, Beijing, China
- GBA Research Innovation Institute for Nanotechnology, Guangzhou, Guangdong Province, China
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26
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Leo S, Cetiner OF, Pittet LF, Messina NL, Jakob W, Falquet L, Curtis N, Zimmermann P. Metagenomics analysis of the neonatal intestinal resistome. Front Pediatr 2023; 11:1169651. [PMID: 37397142 PMCID: PMC10313230 DOI: 10.3389/fped.2023.1169651] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/19/2023] [Accepted: 04/25/2023] [Indexed: 07/04/2023] Open
Abstract
Introduction The intestinal microbiome forms a major reservoir for antibiotic resistance genes (ARGs). Little is known about the neonatal intestinal resistome. Objective The objective of this study was to investigate the intestinal resistome and factors that influence the abundance of ARGs in a large cohort of neonates. Methods Shotgun metagenomics was used to analyse the resistome in stool samples collected at 1 week of age from 390 healthy, term-born neonates who did not receive antibiotics. Results Overall, 913 ARGs belonging to 27 classes were identified. The most abundant ARGs were those conferring resistance to tetracyclines, quaternary ammonium compounds, and macrolide-lincosamide-streptogramin-B. Phylogenetic composition was strongly associated with the resistome composition. Other factors that were associated with the abundance of ARGs were delivery mode, gestational age, birth weight, feeding method, and antibiotics in the last trimester of pregnancy. Sex, ethnicity, probiotic use during pregnancy, and intrapartum antibiotics had little effect on the abundance of ARGs. Conclusion Even in the absence of direct antibiotic exposure, the neonatal intestine harbours a high abundance and a variety of ARGs.
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Affiliation(s)
- Stefano Leo
- Department for Community Health, Faculty of Science and Medicine, University of Fribourg, Fribourg, Switzerland
- Department of Paediatrics, Fribourg Hospital, Fribourg, Switzerland
| | - Omer F. Cetiner
- Istanbul Faculty of Medicine, Istanbul University, Istanbul, Türkiye
| | - Laure F. Pittet
- Department of Paediatrics, The University of Melbourne, Parkville, VIC, Australia
- Infectious Diseases Research Group, Murdoch Children’s Research Institute, Parkville, VIC, Australia
- Pediatric Infectious Diseases Unit, Geneva University Hospitals and Faculty of Medicine, Geneva, Switzerland
| | - Nicole L. Messina
- Department of Paediatrics, The University of Melbourne, Parkville, VIC, Australia
- Infectious Diseases Research Group, Murdoch Children’s Research Institute, Parkville, VIC, Australia
| | - William Jakob
- Microbiology Laboratory, Fribourg Hospital, Fribourg, Switzerland
| | - Laurent Falquet
- Department of Biology, University of Fribourg and Swiss Institute of Bioinformatics, Fribourg, Switzerland
| | - Nigel Curtis
- Department of Paediatrics, The University of Melbourne, Parkville, VIC, Australia
- Infectious Diseases Research Group, Murdoch Children’s Research Institute, Parkville, VIC, Australia
- Infectious Diseases Unit, The Royal Children’s Hospital Melbourne, Parkville, VIC, Australia
| | - Petra Zimmermann
- Department for Community Health, Faculty of Science and Medicine, University of Fribourg, Fribourg, Switzerland
- Department of Paediatrics, Fribourg Hospital, Fribourg, Switzerland
- Department of Paediatrics, The University of Melbourne, Parkville, VIC, Australia
- Infectious Diseases Research Group, Murdoch Children’s Research Institute, Parkville, VIC, Australia
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27
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Abstract
Cardiometabolic disease comprises cardiovascular and metabolic dysfunction and underlies the leading causes of morbidity and mortality, both within the United States and worldwide. Commensal microbiota are implicated in the development of cardiometabolic disease. Evidence suggests that the microbiome is relatively variable during infancy and early childhood, becoming more fixed in later childhood and adulthood. Effects of microbiota, both during early development, and in later life, may induce changes in host metabolism that modulate risk mechanisms and predispose toward the development of cardiometabolic disease. In this review, we summarize the factors that influence gut microbiome composition and function during early life and explore how changes in microbiota and microbial metabolism influence host metabolism and cardiometabolic risk throughout life. We highlight limitations in current methodology and approaches and outline state-of-the-art advances, which are improving research and building toward refined diagnosis and treatment options in microbiome-targeted therapies.
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Affiliation(s)
- Curtis L Gabriel
- Division of Gastroenterology, Hepatology and Nutrition (C.L.G.), Vanderbilt University Medical Center, Nashville
- Tennessee Center for AIDS Research (C.L.G.), Vanderbilt University Medical Center, Nashville
| | - Jane F Ferguson
- Division of Cardiovascular Medicine (J.F.F.), Vanderbilt University Medical Center, Nashville
- Vanderbilt Microbiome Innovation Center (J.F.F.), Vanderbilt University Medical Center, Nashville
- Vanderbilt Institute for Infection, Immunology, and Inflammation (J.F.F.), Vanderbilt University Medical Center, Nashville
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28
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Ijaz MU, Vaziri F, Wan YJY. Effects of Bacillus Calmette-Guérin on immunometabolism, microbiome and liver diseases ⋆. LIVER RESEARCH 2023; 7:116-123. [PMID: 38223885 PMCID: PMC10786626 DOI: 10.1016/j.livres.2023.05.001] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/14/2022] [Revised: 02/22/2023] [Accepted: 05/16/2023] [Indexed: 01/16/2024]
Abstract
Metabolic diseases have overtaken infectious diseases as the most serious public health issue and economic burden in most countries. Moreover, metabolic diseases increase the risk of having infectious diseases. The treatment of metabolic disease may require a long-term strategy of taking multiple medications, which can be costly and have side effects. Attempts to expand the therapeutic use of vaccination to prevent or treat metabolic diseases have attracted significant interest. A growing body of evidence indicates that Bacillus Calmette-Guérin (BCG) offers protection against non-infectious diseases. The non-specific effects of BCG occur likely due to the induction of trained immunity. In this regard, understanding how BCG influences the development of chronic metabolic health including liver diseases would be important. This review focuses on research on BCG, the constellation of disorders associated with metabolic health issues including liver diseases and diabetes as well as how BCG affects the gut microbiome, immunity, and metabolism.
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Affiliation(s)
- Muhammad Umair Ijaz
- Department of Medical Pathology and Laboratory Medicine, University of California Davis School of Medicine, Sacramento, CA, USA
| | - Farzam Vaziri
- Department of Medical Pathology and Laboratory Medicine, University of California Davis School of Medicine, Sacramento, CA, USA
| | - Yu-Jui Yvonne Wan
- Department of Medical Pathology and Laboratory Medicine, University of California Davis School of Medicine, Sacramento, CA, USA
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29
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Oh S, Seo H. Dietary intervention with functional foods modulating gut microbiota for improving the efficacy of COVID-19 vaccines. Heliyon 2023; 9:e15668. [PMID: 37124341 PMCID: PMC10121067 DOI: 10.1016/j.heliyon.2023.e15668] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2023] [Revised: 04/17/2023] [Accepted: 04/18/2023] [Indexed: 05/02/2023] Open
Abstract
Dysbiosis of the gut microbiota with aging contributes to a reduction in important cross-feeding bacterial reactions in the gut and immunosenescence, which could contribute to a decrease in vaccine efficacy. Fever, cough, and fatigue are the main signs of coronavirus disease 2019 (COVID-19); however, some patients with COVID-19 present with gastrointestinal symptoms. COVID-19 vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is one of the best measures to reduce SARS-CoV-2 infection rates and the severity of COVID-19. The immunogenicity of COVID-19 vaccines is influenced by the composition of the gut microbiota, and the immune response to COVID-19 vaccines decreases with age. In this review, we discuss gut microbiota dysbiosis and immunosenescence in the older adults, the role of gut microbiota in improving the efficacy of COVID-19 vaccines, and dietary interventions to improve the efficacy of COVID-19 vaccines in the older adults.
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Affiliation(s)
- Soyoung Oh
- Infectious Disease Research Center, Citizen's Health Bureau, Seoul Metropolitan Government, 110, Sejong-daero, Jung-gu, Seoul, 04524, Republic of Korea
| | - Haesook Seo
- Infectious Disease Research Center, Citizen's Health Bureau, Seoul Metropolitan Government, 110, Sejong-daero, Jung-gu, Seoul, 04524, Republic of Korea
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30
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Zimmermann P. The immunological interplay between vaccination and the intestinal microbiota. NPJ Vaccines 2023; 8:24. [PMID: 36823142 PMCID: PMC9947885 DOI: 10.1038/s41541-023-00627-9] [Citation(s) in RCA: 17] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2023] [Accepted: 02/16/2023] [Indexed: 02/25/2023] Open
Affiliation(s)
- Petra Zimmermann
- Department for Community Health, Faculty of Science and Medicine, University of Fribourg, Fribourg, Switzerland. .,Department of Paediatrics, Fribourg Hospital, Fribourg, Switzerland. .,Department of Paediatrics, The University of Melbourne, Parkville, VIC, Australia. .,Infectious Diseases Research Group, Murdoch Children's Research Institute, Parkville, VIC, Australia.
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31
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Morens DM, Taubenberger JK, Fauci AS. Rethinking next-generation vaccines for coronaviruses, influenzaviruses, and other respiratory viruses. Cell Host Microbe 2023; 31:146-157. [PMID: 36634620 PMCID: PMC9832587 DOI: 10.1016/j.chom.2022.11.016] [Citation(s) in RCA: 92] [Impact Index Per Article: 46.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2022] [Revised: 10/26/2022] [Accepted: 11/29/2022] [Indexed: 01/13/2023]
Abstract
Viruses that replicate in the human respiratory mucosa without infecting systemically, including influenza A, SARS-CoV-2, endemic coronaviruses, RSV, and many other "common cold" viruses, cause significant mortality and morbidity and are important public health concerns. Because these viruses generally do not elicit complete and durable protective immunity by themselves, they have not to date been effectively controlled by licensed or experimental vaccines. In this review, we examine challenges that have impeded development of effective mucosal respiratory vaccines, emphasizing that all of these viruses replicate extremely rapidly in the surface epithelium and are quickly transmitted to other hosts, within a narrow window of time before adaptive immune responses are fully marshaled. We discuss possible approaches to developing next-generation vaccines against these viruses, in consideration of several variables such as vaccine antigen configuration, dose and adjuventation, route and timing of vaccination, vaccine boosting, adjunctive therapies, and options for public health vaccination polices.
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Affiliation(s)
- David M. Morens
- Office of the Director, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
| | - Jeffery K. Taubenberger
- Viral Pathogenesis and Evolution Section, Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA,Corresponding author
| | - Anthony S. Fauci
- Office of the Director, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
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32
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HEMMI J, MAKINO S, YOKOO T, KANO H, ASAMI Y, TAKEDA K, SUZUKI Y, KAWAI S, NAGAOKA I, SAWAKI K, OKUMURA K. Consumption of yogurt fermented with Lactobacillus delbrueckii ssp. bulgaricus OLL1073R-1 augments serum antibody titers against seasonal influenza vaccine in healthy adults. BIOSCIENCE OF MICROBIOTA, FOOD AND HEALTH 2023; 42:73-80. [PMID: 36660594 PMCID: PMC9816052 DOI: 10.12938/bmfh.2022-037] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/16/2022] [Accepted: 09/13/2022] [Indexed: 11/06/2022]
Abstract
Seasonal influenza is a major upper respiratory tract infection occurring in winter. Vaccination is the best method for preventing this infection. We conducted two randomized, double-blind, placebo-controlled trials to examine whether consumption of yogurt fermented with Lactobacillus delbrueckii ssp. bulgaricus OLL1073R-1, which has been reported to reduce the risk of catching the common cold, augments serum antibody titers against seasonal influenza vaccines. In the first trial, which included university students, serum antibody titers against influenza A (H3N2) and B viruses were significantly higher in the yogurt group than in the placebo group. According to the guidelines established by the European Medicines Agency (EMA) for the assessment of vaccines, the seroconversion rate and mean geometric increase of influenza A (H3N2) and seroprotection of influenza B met the criteria only in the yogurt group. In the second trial, which included healthy adults, serum antibody titers against influenza A (H1N1) and B viruses were significantly higher in the yogurt group than in the placebo group. The seroconversion rate and mean geometric increase of influenza B met the EMA criteria only in the yogurt group. Furthermore, the cumulative days of ill health, such as throat complaints, upper respiratory inflammation, and cold, were significantly lower in the yogurt group than in the placebo group. Therefore, daily intake of yogurt fermented with L. bulgaricus OLL1073R-1 could reduce the duration of symptoms caused by respiratory infections and act as a mucosal adjuvant enhancing acquired immune responses against vaccines, leading to the improvement of public health.
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Affiliation(s)
- Jun HEMMI
- Food Microbiology and Function Research Laboratories, R&D
Division, Meiji Co., Ltd., 1-29-1 Nanakuni, Hachioji, Tokyo 192-0919, Japan
| | - Seiya MAKINO
- Food Microbiology and Function Research Laboratories, R&D
Division, Meiji Co., Ltd., 1-29-1 Nanakuni, Hachioji, Tokyo 192-0919, Japan,Department of Biofunctional Microbiota, Graduate School of
Medicine, Juntendo University, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan,*Corresponding author. Seiya Makino (E-mail: )
| | - Takehiro YOKOO
- Food Microbiology and Function Research Laboratories, R&D
Division, Meiji Co., Ltd., 1-29-1 Nanakuni, Hachioji, Tokyo 192-0919, Japan
| | - Hiroshi KANO
- Food Microbiology and Function Research Laboratories, R&D
Division, Meiji Co., Ltd., 1-29-1 Nanakuni, Hachioji, Tokyo 192-0919, Japan,Department of Biofunctional Microbiota, Graduate School of
Medicine, Juntendo University, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan
| | - Yukio ASAMI
- Food Microbiology and Function Research Laboratories, R&D
Division, Meiji Co., Ltd., 1-29-1 Nanakuni, Hachioji, Tokyo 192-0919, Japan
| | - Kazuyoshi TAKEDA
- Department of Biofunctional Microbiota, Graduate School of
Medicine, Juntendo University, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan,Laboratory of Cell Biology, Research Support Center, Graduate
School of Medicine, Juntendo University, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421,
Japan
| | - Yoshio SUZUKI
- Graduate School of Health and Sports Science, Juntendo
University, 1-1 Hiragagakuendai, Inzai, Chiba 270-1695, Japan
| | - Sachio KAWAI
- Graduate School of Health and Sports Science, Juntendo
University, 1-1 Hiragagakuendai, Inzai, Chiba 270-1695, Japan
| | - Isao NAGAOKA
- Department of Host Defense and Biochemical Research, Graduate
School of Medicine, Juntendo University, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421,
Japan
| | - Keisuke SAWAKI
- Graduate School of Health and Sports Science, Juntendo
University, 1-1 Hiragagakuendai, Inzai, Chiba 270-1695, Japan
| | - Ko OKUMURA
- Department of Biofunctional Microbiota, Graduate School of
Medicine, Juntendo University, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan,Atopy (Allergy) Research Center, Graduate School of Medicine,
Juntendo University, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan
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Basudan AM. The Role of Immune Checkpoint Inhibitors in Cancer Therapy. Clin Pract 2022; 13:22-40. [PMID: 36648843 PMCID: PMC9844484 DOI: 10.3390/clinpract13010003] [Citation(s) in RCA: 42] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2022] [Revised: 12/18/2022] [Accepted: 12/22/2022] [Indexed: 12/29/2022] Open
Abstract
Over the years, immune checkpoint inhibitors (CPIs) have become a powerful treatment strategy in the field of cancer immunotherapy. In the last decade, the number of FDA-approved CPIs has been increasing prominently, opening new horizons for the treatment of a wide range of tumor types. Pointedly, three immune checkpoint molecules have been under extensive research, which include cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed cell death protein-1 (PD-1) and its ligand-1 (PD-L1). Despite remarkable success, not all patients respond positively to therapy, which highlights the complexity of the tumor microenvironment (TME) and immune system. This has led to the identification of molecular biomarkers to predict response and toxicity. In addition, there has been an emerging focus on developing new delivery and targeting approaches for better drug efficacy and potency. In this review, we highlight the mechanism of action of major CPIs, their clinical impact, variation in effectiveness, response prediction, updated clinical indications, current challenges and limitations, promising novel approaches, and future directions.
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Affiliation(s)
- Ahmed M Basudan
- Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Saud University, Riyadh 12372, Saudi Arabia
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Bacorn M, Romero-Soto HN, Levy S, Chen Q, Hourigan SK. The Gut Microbiome of Children during the COVID-19 Pandemic. Microorganisms 2022; 10:microorganisms10122460. [PMID: 36557713 PMCID: PMC9783902 DOI: 10.3390/microorganisms10122460] [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: 11/19/2022] [Revised: 12/07/2022] [Accepted: 12/09/2022] [Indexed: 12/15/2022] Open
Abstract
The gut microbiome has been shown to play a critical role in maintaining a healthy state. Dysbiosis of the gut microbiome is involved in modulating disease severity and potentially contributes to long-term outcomes in adults with COVID-19. Due to children having a significantly lower risk of severe illness and limited sample availability, much less is known about the role of the gut microbiome in children with COVID-19. It is well recognized that the developing gut microbiome of children differs from that of adults, but it is unclear if this difference contributes to the different clinical presentations and complications. In this review, we discuss the current knowledge of the gut microbiome in children with COVID-19, with gut microbiome dysbiosis being found in pediatric COVID-19 but specific taxa change often differing from those described in adults. Additionally, we discuss possible mechanisms of how the gut microbiome may mediate the presentation and complications of COVID-19 in children and the potential role for microbial therapeutics.
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35
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Che Y, Fu S, Wang H, Suo J, Chen C, Pu D, Li C, Yang Y. Correlation of the Gut Microbiota and Antitumor Immune Responses Induced by a Human Papillomavirus Therapeutic Vaccine. ACS Infect Dis 2022; 8:2494-2504. [PMID: 36342280 DOI: 10.1021/acsinfecdis.2c00305] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
Abstract
Human papillomavirus (HPV) is the most common sexually transmitted pathogen worldwide and the major risk factor for cervical cancer. According to our previous study, antitumor immune responses induced by a therapeutic vaccine based on HPV E7 peptide are highly variable among individuals. Many studies have demonstrated that the discrepancy in the gut microbiota is an important factor in the development and regulation of the immune system. Therefore, we performed a systematic comparative analysis of gut microbiota in two groups of mice with significant differences in antitumor effects induced by the vaccine, as well as the correlation between immune cells and gut microbiota. We divided the mice into group A, in which the tumor continued growing, and group B, in which the tumor volume was significantly reduced. In group B mice, the vaccination induced a stronger antitumor activity with significantly enhanced IFN-γ-producing CD4+ and CD8+ T lymphocytes, as well as decreased immunosuppressive cells. A detailed gut microbiota analysis revealed a positive Spearman correlation between the percentage of CD8+ T cells and the relative abundance of Corynebacteriales, Parabacteroides, and Bacteroides_sp. Furthermore, the percentage of CD4+ and CD8+ T cells negatively correlated with the abundance of Proteobacteria and Bilophila. By contrast, the abundance of Proteobacteria, Desulfovibrio, and Bilophila positively correlated with the percentage of myeloid-derived suppressor cells (MDSCs), regulatory T cells (Tregs), and type 2-polarized tumor-associated macrophages (M2-TAMs). Overall, the composition of gut microbiota is related to vaccine-induced antitumor effects, and there is a correlation between some gut bacteria and vaccine-induced immune responses.
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Affiliation(s)
- Yuxin Che
- Department of Microbiology and Parasitology, College of Basic Medical Science, China Medical University, Shenyang 110122, China.,Department of Biochemistry & Molecular Biology, Shanxi Medical University, Taiyuan 030001, China
| | - Shihan Fu
- International School, Beijing University of Posts and Telecommunications, Beijing 100876, China
| | - Huan Wang
- Nursing College, Jinzhou Medical University, Jinzhou 121001, China
| | - Jinguo Suo
- Department of Microbiology and Parasitology, College of Basic Medical Science, China Medical University, Shenyang 110122, China
| | - Chunyan Chen
- Department of Microbiology and Parasitology, College of Basic Medical Science, China Medical University, Shenyang 110122, China
| | - Dan Pu
- Department of Microbiology and Parasitology, College of Basic Medical Science, China Medical University, Shenyang 110122, China
| | - Can Li
- Department of Microbiology and Parasitology, College of Basic Medical Science, China Medical University, Shenyang 110122, China
| | - Yang Yang
- Department of Microbiology and Parasitology, College of Basic Medical Science, China Medical University, Shenyang 110122, China
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Zhang L, Xiang Y, Li Y, Zhang J. Gut microbiome in multiple myeloma: Mechanisms of progression and clinical applications. Front Immunol 2022; 13:1058272. [PMID: 36569873 PMCID: PMC9771691 DOI: 10.3389/fimmu.2022.1058272] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2022] [Accepted: 11/15/2022] [Indexed: 12/13/2022] Open
Abstract
The gut commensal microbes modulate human immunity and metabolism through the production of a large number of metabolites, which act as signaling molecules and substrates of metabolic reactions in a diverse range of biological processes. There is a growing appreciation for the importance of immunometabolic mechanisms of the host-gut microbiota interactions in various malignant tumors. Emerging studies have suggested intestinal microbiota contributes to the progression of multiple myeloma. In this review, we summarized the current understanding of the gut microbiome in MM progression and treatment, and the influence of alterations in gut microbiota on treatment response and treatment-related toxicity and complications in MM patients undergoing hematopoietic stem cell transplantation (HSCT). Furthermore, we discussed the impact of gut microbiota-immune system interactions in tumor immunotherapy, focusing on tumor vaccine immunotherapy, which may be an effective approach to improve anti-myeloma efficacy.
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Affiliation(s)
- Liuyun Zhang
- Department of Laboratory Medicine and Sichuan Provincial Key Laboratory for Human Disease Gene Study, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, China,School of Medicine, University of Electronic Science and Technology of China, Chengdu, China
| | - Yunhui Xiang
- Department of Laboratory Medicine and Sichuan Provincial Key Laboratory for Human Disease Gene Study, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, China,School of Medicine, University of Electronic Science and Technology of China, Chengdu, China
| | - Yanying Li
- Department of Laboratory Medicine and Sichuan Provincial Key Laboratory for Human Disease Gene Study, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, China,School of Medicine, University of Electronic Science and Technology of China, Chengdu, China
| | - Juan Zhang
- Department of Laboratory Medicine and Sichuan Provincial Key Laboratory for Human Disease Gene Study, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, China,*Correspondence: Juan Zhang,
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Chin N, Narayan NR, Méndez-Lagares G, Ardeshir A, Chang WLW, Deere JD, Fontaine JH, Chen C, Kieu HT, Lu W, Barry PA, Sparger EE, Hartigan-O'Connor DJ. Cytomegalovirus infection disrupts the influence of short-chain fatty acid producers on Treg/Th17 balance. MICROBIOME 2022; 10:168. [PMID: 36210471 PMCID: PMC9549678 DOI: 10.1186/s40168-022-01355-3] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/13/2022] [Accepted: 08/15/2022] [Indexed: 06/01/2023]
Abstract
BACKGROUND Both the gut microbiota and chronic viral infections have profound effects on host immunity, but interactions between these influences have been only superficially explored. Cytomegalovirus (CMV), for example, infects approximately 80% of people globally and drives significant changes in immune cells. Similarly, certain gut-resident bacteria affect T-cell development in mice and nonhuman primates. It is unknown if changes imposed by CMV on the intestinal microbiome contribute to immunologic effects of the infection. RESULTS We show that rhesus cytomegalovirus (RhCMV) infection is associated with specific differences in gut microbiota composition, including decreased abundance of Firmicutes, and that the extent of microbial change was associated with immunologic changes including the proliferation, differentiation, and cytokine production of CD8+ T cells. Furthermore, RhCMV infection disrupted the relationship between short-chain fatty acid producers and Treg/Th17 balance observed in seronegative animals, showing that some immunologic effects of CMV are due to disruption of previously existing host-microbe relationships. CONCLUSIONS Gut microbes have an important influence on health and disease. Diet is known to shape the microbiota, but the influence of concomitant chronic viral infections is unclear. We found that CMV influences gut microbiota composition to an extent that is correlated with immunologic changes in the host. Additionally, pre-existing correlations between immunophenotypes and gut microbes can be subverted by CMV infection. Immunologic effects of CMV infection on the host may therefore be mediated by two different mechanisms involving gut microbiota. Video Abstract.
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Affiliation(s)
- Ning Chin
- California National Primate Research Center, University of California, Davis, Davis, USA
- Department of Medical Microbiology and Immunology, School of Medicine, University of California, Davis, Davis, USA
| | - Nicole R Narayan
- Department of Medical Microbiology and Immunology, School of Medicine, University of California, Davis, Davis, USA
| | - Gema Méndez-Lagares
- California National Primate Research Center, University of California, Davis, Davis, USA
- Department of Medical Microbiology and Immunology, School of Medicine, University of California, Davis, Davis, USA
| | - Amir Ardeshir
- California National Primate Research Center, University of California, Davis, Davis, USA
| | - W L William Chang
- California National Primate Research Center, University of California, Davis, Davis, USA
- Department of Medical Microbiology and Immunology, School of Medicine, University of California, Davis, Davis, USA
| | - Jesse D Deere
- California National Primate Research Center, University of California, Davis, Davis, USA
- Department of Medical Microbiology and Immunology, School of Medicine, University of California, Davis, Davis, USA
| | - Justin H Fontaine
- California National Primate Research Center, University of California, Davis, Davis, USA
- Department of Medical Microbiology and Immunology, School of Medicine, University of California, Davis, Davis, USA
| | - Connie Chen
- Department of Medical Microbiology and Immunology, School of Medicine, University of California, Davis, Davis, USA
| | - Hung T Kieu
- California National Primate Research Center, University of California, Davis, Davis, USA
- Department of Medical Microbiology and Immunology, School of Medicine, University of California, Davis, Davis, USA
| | - Wenze Lu
- California National Primate Research Center, University of California, Davis, Davis, USA
- Department of Medical Microbiology and Immunology, School of Medicine, University of California, Davis, Davis, USA
| | - Peter A Barry
- Center for Immunology and Infectious Diseases, University of California, Davis, Davis, USA
| | - Ellen E Sparger
- Department of Medicine and Epidemiology, School of Veterinary Medicine, University of California, Davis, Davis, USA
| | - Dennis J Hartigan-O'Connor
- California National Primate Research Center, University of California, Davis, Davis, USA.
- Department of Medical Microbiology and Immunology, School of Medicine, University of California, Davis, Davis, USA.
- Division of Experimental Medicine, Department of Medicine, University of California, San Francisco, San Francisco, USA.
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Transplantation of maternal intestinal flora to the newborn after elective cesarean section (SECFLOR): study protocol for a double blinded randomized controlled trial. BMC Pediatr 2022; 22:565. [PMID: 36175995 PMCID: PMC9521560 DOI: 10.1186/s12887-022-03609-3] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/11/2021] [Accepted: 09/14/2022] [Indexed: 11/24/2022] Open
Abstract
Background A complication of elective cesarean section (CS) delivery is its interference with the normal intestinal colonization of the infant, affecting the immune and metabolic signaling in early life— a process that has been associated with long-term morbidity, such as allergy and diabetes. We evaluate, in CS-delivered infants, whether the normal intestinal microbiome and its early life development can be restored by immediate postnatal transfer of maternal fecal microbiota (FMT) to the newborn, and how this procedure influences the maturation of the immune system. Methods Sixty healthy mothers with planned elective CS are recruited and screened thoroughly for infections. A maternal fecal sample is taken prior to delivery and processed according to a transplantation protocol. After double blinded randomization, half of the newborns will receive a diluted aliquot of their own mother’s stool orally administered in breast milk during the first feeding while the other half will be similarly treated with a placebo. The infants are clinically followed, and fecal samples are gathered weekly until the age of 4 weeks, then at the ages of 8 weeks, 3, 6, 12 and 24 months. The parents fill in questionnaires until the age of 24 months. Blood samples are taken at the age of 2–3 days and 3, 6, 12 and 24 months to assess development of major immune cell populations and plasma proteins throughout the first years of life. Discussion This is the first study to assess long-time effects on the intestinal microbiome and the development of immune system of a maternal fecal transplant given to term infants born by CS. Trial registration ClinicalTrials.gov NCT04173208, registration date 21.11.2019. Supplementary Information The online version contains supplementary material available at 10.1186/s12887-022-03609-3.
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Valentino MS, Esposito C, Colosimo S, Caprio AM, Puzone S, Guarino S, Marzuillo P, Miraglia del Giudice E, Di Sessa A. Gut microbiota and COVID-19: An intriguing pediatric perspective. World J Clin Cases 2022; 10:8076-8087. [PMID: 36159525 PMCID: PMC9403663 DOI: 10.12998/wjcc.v10.i23.8076] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/20/2022] [Revised: 06/14/2022] [Accepted: 07/11/2022] [Indexed: 02/06/2023] Open
Abstract
Gastrointestinal (GI) involvement has been reported in approximately 50% of patients with coronavirus disease 2019 (COVID-19), which is due to the pathogenic role of inflammation and the intestinal function of the angiotensin-converting enzyme 2 and its receptor. Accumulating adult data has pointed out that gut dysbiosis might occur in these patients with a potential impact on the severity of the disease, however the role of gut microbiota in susceptibility and severity of COVID-19 disease in children is still poorly known. During the last decades, the crosstalk between gut and lung has been largely recognized resulting in the concept of "gut-lung axis" as a central player in modulating the development of several diseases. Both organs are involved in the common mucosal immune system (including bronchus-associated and gut-associated lymphoid tissues) and their homeostasis is crucial for human health. In this framework, it has been found that the role of GI dysbiosis is affecting the homeostasis of the gut-liver axis. Of note, a gut microbiome imbalance has been linked to COVID-19 severity in adult subjects, but it remains to be clarified. Based on the increased risk of inflammatory diseases in children with COVID-19, the potential correlation between gut microbiota dysfunction and COVID-19 needs to be studied in this population. We aimed to summarize the most recent evidence on this striking aspect of COVID-19 in childhood.
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Affiliation(s)
- Maria Sole Valentino
- Department of Woman, Child, and General and Specialized Surgery, University of Campania Luigi Vanvitelli, Naples 80138, Italy
| | - Claudia Esposito
- Department of Woman, Child, and General and Specialized Surgery, University of Campania Luigi Vanvitelli, Naples 80138, Italy
| | - Simone Colosimo
- Department of Woman, Child, and General and Specialized Surgery, University of Campania Luigi Vanvitelli, Naples 80138, Italy
| | - Angela Maria Caprio
- Department of Woman, Child, and General and Specialized Surgery, University of Campania Luigi Vanvitelli, Naples 80138, Italy
| | - Simona Puzone
- Department of Woman, Child, and General and Specialized Surgery, University of Campania Luigi Vanvitelli, Naples 80138, Italy
| | - Stefano Guarino
- Department of Woman, Child, and General and Specialized Surgery, University of Campania Luigi Vanvitelli, Naples 80138, Italy
| | - Pierluigi Marzuillo
- Department of Woman, Child, and General and Specialized Surgery, University of Campania Luigi Vanvitelli, Naples 80138, Italy
| | - Emanuele Miraglia del Giudice
- Department of Woman, Child, and General and Specialized Surgery, University of Campania Luigi Vanvitelli, Naples 80138, Italy
| | - Anna Di Sessa
- Department of Woman, Child, and General and Specialized Surgery, University of Campania Luigi Vanvitelli, Naples 80138, Italy
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Isolation and Identification of Lactococcus lactis and Weissella cibaria Strains from Fermented Beetroot and an Investigation of Their Properties as Potential Starter Cultures and Probiotics. Foods 2022; 11:foods11152257. [PMID: 35954024 PMCID: PMC9368051 DOI: 10.3390/foods11152257] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2022] [Revised: 07/15/2022] [Accepted: 07/26/2022] [Indexed: 01/25/2023] Open
Abstract
The presence of certain microorganisms in dairy products or silage is highly desirable. Among them are probiotic strains of lactic acid bacteria (LAB), which show many beneficial features, including antimicrobial properties that support the development of beneficial microflora; in addition, owing to their biochemical activity, they influence the nutritional, dietary, and organoleptic properties of food products. Before being placed on the market, each strain requires separate testing to determine its probiotic properties and effectiveness. The aim of this study was to isolate LAB strains from a pickled beetroot sample that could be used in the dairy industry and with the potential to be considered as a probiotic in the future. Two strains identified using the MALDI technique were selected—Lactococcus lactis and Weissella cibaria. The optimal growth conditions of the strains were determined, and their proteolytic properties were assessed with the use of the o-PA reagent and spectrophotometry. The lipid profile was analyzed using the SALDI (surface-assisted laser desorption/ionization) technique and silver nanoparticles. High-performance liquid chromatography was used to assess the ability of the strains to synthesize beneficial metabolites, such as B vitamins (B2, B3, and B9) or lactic acid, and gas chromatography was used to analyze the substances responsible for organoleptic properties. Moreover, the ability to inhibit the growth of pathogenic strains was also tested in the selected strains. Both tested strains demonstrated the desired properties of starter cultures for future use in functional food production, showing that fermented plant products can serve as valuable potential probiotic sources.
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Priddy FH, Williams M, Carson S, Lavender B, Mathieson J, Frampton C, Moreland NJ, McGregor R, Williams G, Brewerton M, Gell K, Ussher J, Le Gros G. Immunogenicity of BNT162b2 COVID-19 vaccine in New Zealand adults. Vaccine 2022; 40:5050-5059. [PMID: 35868948 PMCID: PMC9273612 DOI: 10.1016/j.vaccine.2022.07.009] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2022] [Revised: 06/30/2022] [Accepted: 07/07/2022] [Indexed: 01/07/2023]
Abstract
Background There is very little known about SARS-CoV-2 vaccine immune responses in New Zealand populations at greatest risk for serious COVID-19 disease. Methods This prospective cohort study assessed immunogenicity in BNT162b2 mRNA vaccine recipients in New Zealand without previous COVID-19, with enrichment for Māori, Pacific peoples, older adults ≥ 65 years of age, and those with co-morbidities. Serum samples were analysed at baseline and 28 days after second dose for presence of quantitative anti-S IgG by chemiluminescent microparticle immunoassay and for neutralizing capacity against Wuhan, Beta, Delta, and Omicron BA.1 strains using a surrogate viral neutralisation assay. Results 285 adults with median age of 52 years were included. 55% were female, 30% were Māori, 28% were Pacific peoples, and 26% were ≥ 65 years of age. Obesity, cardiac and pulmonary disease and diabetes were more common than in the general population. All participants received 2 doses of BNT162b2 vaccine. At 28 days after second vaccination, 99.6% seroconverted to the vaccine, and anti-S IgG and neutralising antibody levels were high across gender and ethnic groups. IgG and neutralising responses declined with age. Lower responses were associated with age ≥ 75 and diabetes, but not BMI. The ability to neutralise the Omicron BA.1 variant in vitro was severely diminished but maintained against other variants of concern. Conclusions Vaccine antibody responses to BNT162b2 were generally robust and consistent with international data in this COVID-19 naïve cohort with representation of key populations at risk for COVID-19 morbidity. Subsequent data on response to boosters, durability of responses and cellular immune responses should be assessed with attention to elderly adults and diabetics.
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Affiliation(s)
- Frances H Priddy
- Vaccine Alliance Aotearoa New Zealand and Malaghan Institute of Medical Research, PO Box 7060, Wellington 6242, New Zealand.
| | - Michael Williams
- Pacific Clinical Research Network, 1289 Haupapa St, Rotorua 3010, New Zealand
| | - Simon Carson
- Pacific Clinical Research Network, 1289 Haupapa St, Rotorua 3010, New Zealand
| | - Brittany Lavender
- Vaccine Alliance Aotearoa New Zealand and Malaghan Institute of Medical Research, PO Box 7060, Wellington 6242, New Zealand
| | - Julia Mathieson
- Pacific Clinical Research Network, 1289 Haupapa St, Rotorua 3010, New Zealand
| | - Chris Frampton
- University of Otago, 2 Riccarton Ave, Christchurch 8011, New Zealand
| | - Nicole J Moreland
- University of Auckland, 2 Park Rd, Grafton Auckland 1023, New Zealand
| | - Reuben McGregor
- University of Auckland, 2 Park Rd, Grafton Auckland 1023, New Zealand
| | - Georgia Williams
- Pacific Clinical Research Network, 1289 Haupapa St, Rotorua 3010, New Zealand
| | - Maia Brewerton
- Vaccine Alliance Aotearoa New Zealand and Malaghan Institute of Medical Research, PO Box 7060, Wellington 6242, New Zealand; Department of Clinical Immunology & Allergy, Auckland City Hospital, 2 Park Rd, Grafton Auckland 1023, New Zealand
| | - Katie Gell
- Vaccine Alliance Aotearoa New Zealand and Malaghan Institute of Medical Research, PO Box 7060, Wellington 6242, New Zealand
| | - James Ussher
- Vaccine Alliance Aotearoa New Zealand and University of Otago, 362 Leith St, Dunedin 9016 New Zealand
| | - Graham Le Gros
- Vaccine Alliance Aotearoa New Zealand and Malaghan Institute of Medical Research, PO Box 7060, Wellington 6242, New Zealand
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Gulliver EL, Young RB, Chonwerawong M, D'Adamo GL, Thomason T, Widdop JT, Rutten EL, Rossetto Marcelino V, Bryant RV, Costello SP, O'Brien CL, Hold GL, Giles EM, Forster SC. Review article: the future of microbiome-based therapeutics. Aliment Pharmacol Ther 2022; 56:192-208. [PMID: 35611465 PMCID: PMC9322325 DOI: 10.1111/apt.17049] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/24/2022] [Revised: 03/29/2022] [Accepted: 05/12/2022] [Indexed: 12/12/2022]
Abstract
BACKGROUND From consumption of fermented foods and probiotics to emerging applications of faecal microbiota transplantation, the health benefit of manipulating the human microbiota has been exploited for millennia. Despite this history, recent technological advances are unlocking the capacity for targeted microbial manipulation as a novel therapeutic. AIM This review summarises the current developments in microbiome-based medicines and provides insight into the next steps required for therapeutic development. METHODS Here we review current and emerging approaches and assess the capabilities and weaknesses of these technologies to provide safe and effective clinical interventions. Key literature was identified through Pubmed searches with the following key words, 'microbiome', 'microbiome biomarkers', 'probiotics', 'prebiotics', 'synbiotics', 'faecal microbiota transplant', 'live biotherapeutics', 'microbiome mimetics' and 'postbiotics'. RESULTS Improved understanding of the human microbiome and recent technological advances provide an opportunity to develop a new generation of therapies. These therapies will range from dietary interventions, prebiotic supplementations, single probiotic bacterial strains, human donor-derived faecal microbiota transplants, rationally selected combinations of bacterial strains as live biotherapeutics, and the beneficial products or effects produced by bacterial strains, termed microbiome mimetics. CONCLUSIONS Although methods to identify and refine these therapeutics are continually advancing, the rapid emergence of these new approaches necessitates accepted technological and ethical frameworks for measurement, testing, laboratory practices and clinical translation.
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Affiliation(s)
- Emily L. Gulliver
- Centre for Innate Immunity and Infectious DiseasesHudson Institute of Medical ResearchClaytonVictoriaAustralia,Department of Molecular and Translational SciencesMonash UniversityClaytonVictoriaAustralia
| | - Remy B. Young
- Centre for Innate Immunity and Infectious DiseasesHudson Institute of Medical ResearchClaytonVictoriaAustralia,Department of Molecular and Translational SciencesMonash UniversityClaytonVictoriaAustralia
| | - Michelle Chonwerawong
- Centre for Innate Immunity and Infectious DiseasesHudson Institute of Medical ResearchClaytonVictoriaAustralia,Department of Molecular and Translational SciencesMonash UniversityClaytonVictoriaAustralia
| | - Gemma L. D'Adamo
- Centre for Innate Immunity and Infectious DiseasesHudson Institute of Medical ResearchClaytonVictoriaAustralia,Department of Molecular and Translational SciencesMonash UniversityClaytonVictoriaAustralia
| | - Tamblyn Thomason
- Centre for Innate Immunity and Infectious DiseasesHudson Institute of Medical ResearchClaytonVictoriaAustralia,Department of Molecular and Translational SciencesMonash UniversityClaytonVictoriaAustralia
| | - James T. Widdop
- Centre for Innate Immunity and Infectious DiseasesHudson Institute of Medical ResearchClaytonVictoriaAustralia,Department of Molecular and Translational SciencesMonash UniversityClaytonVictoriaAustralia
| | - Emily L. Rutten
- Centre for Innate Immunity and Infectious DiseasesHudson Institute of Medical ResearchClaytonVictoriaAustralia,Department of Molecular and Translational SciencesMonash UniversityClaytonVictoriaAustralia
| | - Vanessa Rossetto Marcelino
- Centre for Innate Immunity and Infectious DiseasesHudson Institute of Medical ResearchClaytonVictoriaAustralia,Department of Molecular and Translational SciencesMonash UniversityClaytonVictoriaAustralia
| | - Robert V. Bryant
- Department of GastroenterologyThe Queen Elizabeth HospitalWoodvilleSouth AustraliaAustralia,School of MedicineUniversity of AdelaideAdelaideSouth AustraliaAustralia
| | - Samuel P. Costello
- Department of GastroenterologyThe Queen Elizabeth HospitalWoodvilleSouth AustraliaAustralia,School of MedicineUniversity of AdelaideAdelaideSouth AustraliaAustralia
| | | | - Georgina L. Hold
- Microbiome Research Centre, St George & Sutherland Clinical SchoolUniversity of New South WalesSydneyNew South WalesAustralia
| | - Edward M. Giles
- Centre for Innate Immunity and Infectious DiseasesHudson Institute of Medical ResearchClaytonVictoriaAustralia,Department of Molecular and Translational SciencesMonash UniversityClaytonVictoriaAustralia,Department of PaediatricsMonash UniversityClaytonVictoriaAustralia
| | - Samuel C. Forster
- Centre for Innate Immunity and Infectious DiseasesHudson Institute of Medical ResearchClaytonVictoriaAustralia,Department of Molecular and Translational SciencesMonash UniversityClaytonVictoriaAustralia
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Antigen-bearing outer membrane vesicles as tumour vaccines produced in situ by ingested genetically engineered bacteria. Nat Biomed Eng 2022; 6:898-909. [PMID: 35501399 DOI: 10.1038/s41551-022-00886-2] [Citation(s) in RCA: 116] [Impact Index Per Article: 38.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2021] [Accepted: 03/21/2022] [Indexed: 02/05/2023]
Abstract
The complex gastrointestinal environment and the intestinal epithelial barrier constrain the design and effectiveness of orally administered tumour vaccines. Here we show that outer membrane vesicles (OMVs) fused to a tumour antigen and produced in the intestine by ingested genetically engineered bacteria function as effective tumour vaccines in mice. We modified Escherichia coli to express, under the control of a promoter induced by the monosaccharide arabinose, a specific tumour antigen fused with the protein cytolysin A on the surface of OMVs released by the commensal bacteria. In mice, oral administration of arabinose and the genetically engineered E. coli led to the production of OMVs that crossed the intestinal epithelium into the lamina propria, where they stimulated dendritic cell maturation. In a mouse model of pulmonary metastatic melanoma and in mice bearing subcutaneous colon tumours, the antigen-bearing OMVs inhibited tumour growth and protected the animals against tumour re-challenge. The in situ production of OMVs by genetically modified commensal bacteria for the delivery of stimulatory molecules could be leveraged for the development of other oral vaccines and therapeutics.
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Cheung KS, Lam LK, Hui RWH, Mao X, Zhang RR, Chan KH, Hung IF, Seto WK, Yuen MF. Effect of moderate-to-severe hepatic steatosis on neutralising antibody response among BNT162b2 and CoronaVac recipients. Clin Mol Hepatol 2022; 28:553-564. [PMID: 35545127 PMCID: PMC9293606 DOI: 10.3350/cmh.2022.0082] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/18/2022] [Accepted: 05/06/2022] [Indexed: 11/05/2022] Open
Abstract
Aim Studies of hepatic steatosis (HS) effect on COVID-19 vaccine immunogenicity are lacking. We aimed to compare immunogenicity of BNT162b2 and CoronaVac among moderate/severe HS and control subjects. Patients and Methods 295 subjects who received BNT162b2 or CoronaVac vaccines from five vaccination centers were categorized into moderate/severe HS (controlled attenuation parameter ≥268 dB/m on transient elastography) (n=74) or control (n=221) groups. Primary outcomes were seroconversion rates of neutralising antibody by live virus Microneutralization (vMN) assay (titer ≥10) at day 21 (BNT162b2) or day28 (CoronaVac) and day56 (both). Secondary outcome was highest-tier titer response (top 25% of vMN titer; cutoff: 160 [BNT162b2] and 20 [CoronaVac]) at day 56. Results For BNT162b2 (n=228 [77.3%]), there was no statistical differences in seroconversion rates (71.7% vs 76.6% [day21]; 100% vs 100% [day56]) or vMN GMT (13.2 vs 13.3, [day21]; 91.9 vs 101.4, [day56]) among moderate/severe HS and control groups respectively. However, lower proportion of moderate/severe HS patients had highest-tier response (5.0% vs 15.5%; p=0.037 [day56]). For CoronaVac (n=67 [22.7%]), there was no statistical differences in seroconversion rates (7.1% vs 15.1%, [day21]; 64.3% vs 83.0%, [day56]) or vMN GMT (5.3 vs 5.8,) at day 28. However, moderate/severe HS patients had lower vMN GMT (9.1 vs 14.8, p=0.021) at day 56 with lower proportion having highest-tier response (21.4% vs 52.8%, p=0.036). Conclusion While there was no difference in seroconversion rate between moderate/severe HS and control groups after two doses of vaccine, a lower proportion of moderate/severe HS patients achieved highest-tier response for either BNT162b2 or CoronaVac.
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Affiliation(s)
- Ka Shing Cheung
- Department of Medicine, School of Clinical Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong.,Department of Medicine, The University of Hong Kong-Shenzhen Hospital, Shenzhen, China
| | - Lok Ka Lam
- Department of Medicine, School of Clinical Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong
| | - Rex Wan Hin Hui
- Department of Medicine, School of Clinical Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong
| | - Xianhua Mao
- Department of Medicine, School of Clinical Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong
| | - Ruiqi R Zhang
- Department of Medicine, School of Clinical Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong
| | - Kwok Hung Chan
- Department of Microbiology, The University of Hong Kong, Queen Mary Hospital, Hong Kong
| | - Ivan Fn Hung
- Department of Medicine, School of Clinical Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong
| | - Wai Kay Seto
- Department of Medicine, School of Clinical Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong.,Department of Medicine, The University of Hong Kong-Shenzhen Hospital, Shenzhen, China.,State Key Laboratory of Liver Research, The University of Hong Kong, Hong Kong
| | - Man Fung Yuen
- Department of Medicine, School of Clinical Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong.,State Key Laboratory of Liver Research, The University of Hong Kong, Hong Kong
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Singh P, Forthal DN, Shah M, Bruckner TA. Association between vaccine preventable diseases in children and improved sanitation following a nationwide sanitation campaign in India: an ecological analysis. BMJ Open 2022; 12:e052937. [PMID: 35443943 PMCID: PMC9021782 DOI: 10.1136/bmjopen-2021-052937] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/08/2022] Open
Abstract
OBJECTIVE Persistent exposure to faecal pathogens due to open defecation may cause environmental enteropathy that, in turn, may lead to undernutrition and vaccine failure in under 5-year-old (u5) children. The Swachh Bharat Mission (SBM) programme in India, launched in 2014, aimed to construct toilets for every household nationwide and reduce open defecation. This programme, if successful, had the potential to reduce the burden of four vaccine preventable diseases (VPDs): diphtheria, pertussis, tetanus and measles. We examine whether increased household toilet availability in Indian districts following SBM corresponds with a reduction in diphtheria, pertussis, tetanus and measles in u5 children. DESIGN Observational, ecological study. SETTING 532 districts in 28 Indian states, from 2013 to 2016. PRIMARY OUTCOME AND EXPOSURE We retrieved data on district-level change in the annual incidence (per 1000 u5 children) of four VPDs, from 2013 (pre-SBM) to 2016 (post-SBM). We obtained data on our exposure, the change in the percentage of households with toilets (per district), from three large national surveys conducted in 2013 and 2016. We used linear regression analysis, which controlled for change over time in socioeconomic factors, health system-related covariates and pre-SBM annual incidence of VPDs. RESULTS A one percentage point increase in households with toilets corresponds with 0.33 fewer measle cases per 1000 u5 children in a district (coefficient: -0.33, 95% CI -0.0641 to -0.014; p<0.05). About 12% of this association is mediated by a reduction in u5 stunting. We observe no relation of the exposure with diphtheria, pertussis or tetanus. Findings remain robust to sensitivity analyses. CONCLUSION Rapid improvements in ambient sanitation through increased toilet availability correspond with a reduction in the annual incidence of measles in u5 children. We encourage replication of findings and further research to identify potential pathways by which SBM may reduce measle burden in u5 children.
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Affiliation(s)
- Parvati Singh
- College of Public Health, The Ohio State University, Columbus, Ohio, USA
| | - Donald N Forthal
- School of Medicine, University of California, Irvine, California, USA
| | - Manisha Shah
- Luskin School of Public Affairs, University of California, Los Angeles, California, USA
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Borgognone A, Noguera-Julian M, Oriol B, Noël-Romas L, Ruiz-Riol M, Guillén Y, Parera M, Casadellà M, Duran C, Puertas MC, Català-Moll F, De Leon M, Knodel S, Birse K, Manzardo C, Miró JM, Clotet B, Martinez-Picado J, Moltó J, Mothe B, Burgener A, Brander C, Paredes R. Gut microbiome signatures linked to HIV-1 reservoir size and viremia control. MICROBIOME 2022; 10:59. [PMID: 35410461 PMCID: PMC9004083 DOI: 10.1186/s40168-022-01247-6] [Citation(s) in RCA: 29] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/18/2021] [Accepted: 02/16/2022] [Indexed: 05/28/2023]
Abstract
BACKGROUND The potential role of the gut microbiome as a predictor of immune-mediated HIV-1 control in the absence of antiretroviral therapy (ART) is still unknown. In the BCN02 clinical trial, which combined the MVA.HIVconsv immunogen with the latency-reversing agent romidepsin in early-ART treated HIV-1 infected individuals, 23% (3/13) of participants showed sustained low-levels of plasma viremia during 32 weeks of a monitored ART pause (MAP). Here, we present a multi-omics analysis to identify compositional and functional gut microbiome patterns associated with HIV-1 control in the BCN02 trial. RESULTS Viremic controllers during the MAP (controllers) exhibited higher Bacteroidales/Clostridiales ratio and lower microbial gene richness before vaccination and throughout the study intervention when compared to non-controllers. Longitudinal assessment indicated that the gut microbiome of controllers was enriched in pro-inflammatory bacteria and depleted in butyrate-producing bacteria and methanogenic archaea. Functional profiling also showed that metabolic pathways related to fatty acid and lipid biosynthesis were significantly increased in controllers. Fecal metaproteome analyses confirmed that baseline functional differences were mainly driven by Clostridiales. Participants with high baseline Bacteroidales/Clostridiales ratio had increased pre-existing immune activation-related transcripts. The Bacteroidales/Clostridiales ratio as well as host immune-activation signatures inversely correlated with HIV-1 reservoir size. CONCLUSIONS The present proof-of-concept study suggests the Bacteroidales/Clostridiales ratio as a novel gut microbiome signature associated with HIV-1 reservoir size and immune-mediated viral control after ART interruption. Video abstract.
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Affiliation(s)
- Alessandra Borgognone
- IrsiCaixa AIDS Research Institute, Hospital Universitari Germans Trias i Pujol, Barcelona, Catalonia, Spain.
| | - Marc Noguera-Julian
- IrsiCaixa AIDS Research Institute, Hospital Universitari Germans Trias i Pujol, Barcelona, Catalonia, Spain
- CIBERINFEC, Madrid, Spain
- University of Vic-Central University of Catalonia (UVic-UCC), Vic, Catalonia, Spain
| | - Bruna Oriol
- IrsiCaixa AIDS Research Institute, Hospital Universitari Germans Trias i Pujol, Barcelona, Catalonia, Spain
- Universitat Autonoma de Barcelona (UAB), Barcelona, Catalonia, Spain
| | - Laura Noël-Romas
- Center for Global Health and Diseases, Department of Pathology, Case Western Reserve University, Cleveland, OH, USA
- Department of Obstetrics & Gynecology, University of Manitoba, Winnipeg, Manitoba, Canada
| | - Marta Ruiz-Riol
- IrsiCaixa AIDS Research Institute, Hospital Universitari Germans Trias i Pujol, Barcelona, Catalonia, Spain
- CIBERINFEC, Madrid, Spain
| | - Yolanda Guillén
- Institut Mar d'Investigacions mediques (IMIM), CIBERONC, Barcelona, Catalonia, Spain
| | - Mariona Parera
- IrsiCaixa AIDS Research Institute, Hospital Universitari Germans Trias i Pujol, Barcelona, Catalonia, Spain
| | - Maria Casadellà
- IrsiCaixa AIDS Research Institute, Hospital Universitari Germans Trias i Pujol, Barcelona, Catalonia, Spain
| | - Clara Duran
- IrsiCaixa AIDS Research Institute, Hospital Universitari Germans Trias i Pujol, Barcelona, Catalonia, Spain
- Universitat Autonoma de Barcelona (UAB), Barcelona, Catalonia, Spain
| | - Maria C Puertas
- IrsiCaixa AIDS Research Institute, Hospital Universitari Germans Trias i Pujol, Barcelona, Catalonia, Spain
- CIBERINFEC, Madrid, Spain
| | - Francesc Català-Moll
- IrsiCaixa AIDS Research Institute, Hospital Universitari Germans Trias i Pujol, Barcelona, Catalonia, Spain
| | - Marlon De Leon
- Center for Global Health and Diseases, Department of Pathology, Case Western Reserve University, Cleveland, OH, USA
| | - Samantha Knodel
- Center for Global Health and Diseases, Department of Pathology, Case Western Reserve University, Cleveland, OH, USA
- Department of Obstetrics & Gynecology, University of Manitoba, Winnipeg, Manitoba, Canada
| | - Kenzie Birse
- Center for Global Health and Diseases, Department of Pathology, Case Western Reserve University, Cleveland, OH, USA
- Department of Obstetrics & Gynecology, University of Manitoba, Winnipeg, Manitoba, Canada
| | - Christian Manzardo
- Infectious Diseases Service, Hospital Clinic-Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Catalonia, Spain
| | - José M Miró
- CIBERINFEC, Madrid, Spain
- Infectious Diseases Service, Hospital Clinic-Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Catalonia, Spain
| | - Bonaventura Clotet
- IrsiCaixa AIDS Research Institute, Hospital Universitari Germans Trias i Pujol, Barcelona, Catalonia, Spain
- CIBERINFEC, Madrid, Spain
- University of Vic-Central University of Catalonia (UVic-UCC), Vic, Catalonia, Spain
- Universitat Autonoma de Barcelona (UAB), Barcelona, Catalonia, Spain
- Fight AIDS Foundation, Infectious Diseases Department, Germans Trias i Pujol University Hospital, Barcelona, Catalonia, Spain
- Department of Infectious Diseases Service, Germans Trias i Pujol University Hospital, Barcelona, Catalonia, Spain
| | - Javier Martinez-Picado
- IrsiCaixa AIDS Research Institute, Hospital Universitari Germans Trias i Pujol, Barcelona, Catalonia, Spain
- CIBERINFEC, Madrid, Spain
- University of Vic-Central University of Catalonia (UVic-UCC), Vic, Catalonia, Spain
- Catalan Institution for Research and Advanced Studies (ICREA), Barcelona, Catalonia, Spain
| | - José Moltó
- CIBERINFEC, Madrid, Spain
- Fight AIDS Foundation, Infectious Diseases Department, Germans Trias i Pujol University Hospital, Barcelona, Catalonia, Spain
- Department of Infectious Diseases Service, Germans Trias i Pujol University Hospital, Barcelona, Catalonia, Spain
| | - Beatriz Mothe
- IrsiCaixa AIDS Research Institute, Hospital Universitari Germans Trias i Pujol, Barcelona, Catalonia, Spain
- CIBERINFEC, Madrid, Spain
- University of Vic-Central University of Catalonia (UVic-UCC), Vic, Catalonia, Spain
- Fight AIDS Foundation, Infectious Diseases Department, Germans Trias i Pujol University Hospital, Barcelona, Catalonia, Spain
- Department of Infectious Diseases Service, Germans Trias i Pujol University Hospital, Barcelona, Catalonia, Spain
| | - Adam Burgener
- Center for Global Health and Diseases, Department of Pathology, Case Western Reserve University, Cleveland, OH, USA
- Department of Obstetrics & Gynecology, University of Manitoba, Winnipeg, Manitoba, Canada
- Department of Medicine Solna, Center for Molecular Medicine, Karolinska Institute, Karolinska University Hospital, Stockholm, Sweden
| | - Christian Brander
- IrsiCaixa AIDS Research Institute, Hospital Universitari Germans Trias i Pujol, Barcelona, Catalonia, Spain
- CIBERINFEC, Madrid, Spain
- University of Vic-Central University of Catalonia (UVic-UCC), Vic, Catalonia, Spain
- Catalan Institution for Research and Advanced Studies (ICREA), Barcelona, Catalonia, Spain
| | - Roger Paredes
- IrsiCaixa AIDS Research Institute, Hospital Universitari Germans Trias i Pujol, Barcelona, Catalonia, Spain.
- CIBERINFEC, Madrid, Spain.
- University of Vic-Central University of Catalonia (UVic-UCC), Vic, Catalonia, Spain.
- Universitat Autonoma de Barcelona (UAB), Barcelona, Catalonia, Spain.
- Center for Global Health and Diseases, Department of Pathology, Case Western Reserve University, Cleveland, OH, USA.
- Fight AIDS Foundation, Infectious Diseases Department, Germans Trias i Pujol University Hospital, Barcelona, Catalonia, Spain.
- Department of Infectious Diseases Service, Germans Trias i Pujol University Hospital, Barcelona, Catalonia, Spain.
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Sandionigi A, De Giani A, Tursi F, Michelotti A, Cestone E, Giardina S, Zampolli J, Di Gennaro P. Effectiveness of Multistrain Probiotic Formulation on Common Infectious Disease Symptoms and Gut Microbiota Modulation in Flu-Vaccinated Healthy Elderly Subjects. BIOMED RESEARCH INTERNATIONAL 2022; 2022:3860896. [PMID: 35127941 PMCID: PMC8814717 DOI: 10.1155/2022/3860896] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/15/2021] [Accepted: 12/16/2021] [Indexed: 11/17/2022]
Abstract
The decline of the immune system with aging leads elderly people to be more susceptible to infections, posing high risk for their health. Vaccination is thus important to cope with this risk, even though not always effective. As a strategy to improve protection, adjuvants are used in concomitance with vaccines, however, occasionally producing important side effects. The use of probiotics has been proposed as an alternative to adjuvants due to their efficacy in reducing the risk of common infections through the interactions with the immune system and the gut microbiota. A placebo-controlled, randomized, double-blind, clinical trial was carried out on fifty elderly subjects, vaccinated for influenza, to determine the efficacy of a probiotic mixture in reducing common infection symptoms. The incidence of symptoms was evaluated after 28 days of probiotic intake (namely, T28) and after further 28 days of follow-up (namely, T56). The number of subjects, as well as the number of days with symptoms, was remarkably reduced at T28, and even more at T56 in the probiotic group. Furthermore, the influence of probiotics on immunological parameters was investigated, showing a significant positive improvement of total antioxidant capacity and β-defensin2 levels. Finally, faecal samples collected from participants were used to assess variations in the gut microbiota composition during the study, showing that probiotic intake enhanced the presence of genera related to a healthy status. Therefore, the collected results suggested that the treatment with the selected probiotic mixture could help in reducing common infectious disease symptom incidence through the stimulation of the immune system, improving vaccine efficacy, and modulating the composition of the resident gut microbiota by enhancing beneficial genera.
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Affiliation(s)
- Anna Sandionigi
- Department of Biotechnology and Biosciences, University of Milano-Bicocca, Milano, Italy
| | - Alessandra De Giani
- Department of Biotechnology and Biosciences, University of Milano-Bicocca, Milano, Italy
| | | | | | - Enza Cestone
- Complife Italia Srl, San Martino Siccomario (PV), Italy
| | | | - Jessica Zampolli
- Department of Biotechnology and Biosciences, University of Milano-Bicocca, Milano, Italy
| | - Patrizia Di Gennaro
- Department of Biotechnology and Biosciences, University of Milano-Bicocca, Milano, Italy
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Merra G, Capacci A, Cenname G, Esposito E, Dri M, Di Renzo L, Marchetti M. The "Microbiome": A Protagonist in COVID-19 Era. Microorganisms 2022; 10:296. [PMID: 35208751 PMCID: PMC8879283 DOI: 10.3390/microorganisms10020296] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2021] [Revised: 01/25/2022] [Accepted: 01/25/2022] [Indexed: 02/04/2023] Open
Abstract
Respiratory infections are among the main causes of hospitalization and mortality, particularly in elderly patients [...].
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Affiliation(s)
- Giuseppe Merra
- Section of Clinical Nutrition and Nutrigenomic, Department of Biomedicine and Prevention, University of Rome Tor Vergata, 00133 Rome, Italy; (L.D.R.); (M.M.)
| | - Annunziata Capacci
- Department of Medical and Surgical Sciences, Agostino Gemelli General Hospital Foundation-IRCCS, 00168 Rome, Italy;
| | - Giuseppe Cenname
- Comando Generale Arma Carabinieri, Direzione di Sanità, 00197 Rome, Italy;
| | - Ernesto Esposito
- Department of Human Policies [General Directorate] of Basilicata Region, 85100 Potenza, Italy;
| | - Maria Dri
- Department of Surgical Sciences, School of Applied Medical-Surgical Sciences, University of Rome Tor Vergata, 00133 Rome, Italy;
| | - Laura Di Renzo
- Section of Clinical Nutrition and Nutrigenomic, Department of Biomedicine and Prevention, University of Rome Tor Vergata, 00133 Rome, Italy; (L.D.R.); (M.M.)
| | - Marco Marchetti
- Section of Clinical Nutrition and Nutrigenomic, Department of Biomedicine and Prevention, University of Rome Tor Vergata, 00133 Rome, Italy; (L.D.R.); (M.M.)
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Connor RI, Brickley EB, Wieland-Alter WF, Ackerman ME, Weiner JA, Modlin JF, Bandyopadhyay AS, Wright PF. Mucosal immunity to poliovirus. Mucosal Immunol 2022; 15:1-9. [PMID: 34239028 PMCID: PMC8732262 DOI: 10.1038/s41385-021-00428-0] [Citation(s) in RCA: 32] [Impact Index Per Article: 10.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2021] [Revised: 05/26/2021] [Accepted: 06/14/2021] [Indexed: 02/04/2023]
Abstract
A cornerstone of the global initiative to eradicate polio is the widespread use of live and inactivated poliovirus vaccines in extensive public health campaigns designed to prevent the development of paralytic disease and interrupt transmission of the virus. Central to these efforts is the goal of inducing mucosal immunity able to limit virus replication in the intestine. Recent clinical trials have evaluated new combined regimens of poliovirus vaccines, and demonstrated clear differences in their ability to restrict virus shedding in stool after oral challenge with live virus. Analyses of mucosal immunity accompanying these trials support a critical role for enteric neutralizing IgA in limiting the magnitude and duration of virus shedding. This review summarizes key findings in vaccine-induced intestinal immunity to poliovirus in infants, older children, and adults. The impact of immunization on development and maintenance of protective immunity to poliovirus and the implications for global eradication are discussed.
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Affiliation(s)
- Ruth I Connor
- Department of Pediatrics, Dartmouth-Hitchcock Medical Center, Lebanon, NH, USA
- Department of Microbiology and Immunology, Geisel School of Medicine, Dartmouth College, Hanover, NH, USA
| | - Elizabeth B Brickley
- Department of Infectious Disease Epidemiology, London School of Hygiene & Tropical Medicine, London, UK
| | | | - Margaret E Ackerman
- Department of Microbiology and Immunology, Geisel School of Medicine, Dartmouth College, Hanover, NH, USA
- Thayer School of Engineering, Dartmouth College, Hanover, NH, USA
| | - Joshua A Weiner
- Thayer School of Engineering, Dartmouth College, Hanover, NH, USA
| | | | | | - Peter F Wright
- Department of Pediatrics, Dartmouth-Hitchcock Medical Center, Lebanon, NH, USA.
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Abstract
The microorganisms associated with an organism, the microbiome, have a strong and wide impact in their host biology. In particular, the microbiome modulates both the host defense responses and immunity, thus influencing the fate of infections by pathogens. Indeed, this immune modulation and/or interaction with pathogenic viruses can be essential to define the outcome of viral infections. Understanding the interplay between the microbiome and pathogenic viruses opens future venues to fight viral infections and enhance the efficacy of antiviral therapies. An increasing number of researchers are focusing on microbiome-virus interactions, studying diverse combinations of microbial communities, hosts, and pathogenic viruses. Here, we aim to review these studies, providing an integrative overview of the microbiome impact on viral infection across different pathosystems.
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Affiliation(s)
- Rubén González
- Instituto de Biología Integrativa de Sistemas, Consejo Superior de Investigaciones Científicas-Universitat de València, Paterna, Valencia, Spain
| | - Santiago F. Elena
- Instituto de Biología Integrativa de Sistemas, Consejo Superior de Investigaciones Científicas-Universitat de València, Paterna, Valencia, Spain
- The Santa Fe Institute, Santa Fe, New Mexico, USA
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