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      Research article antibody induction and immune response in nasal cavity by third dose of SARS-CoV-2 mRNA vaccination

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          Abstract

          Background

          The mucosa serves as the first defence against pathogens and facilitates the surveillance and elimination of symbiotic bacteria by mucosal immunity. Recently, the mRNA vaccine against SARS-CoV-2 has been demonstrated to induce secretory antibodies in the oral and nasal cavities in addition to a systemic immune response. However, the mechanism of induced immune stimulation effect on mucosal immunity and commensal bacteria profile remains unclear.

          Methods

          Here, we longitudinally analysed the changing nasal microbiota and both systemic and nasal immune response upon SARS-CoV-2 mRNA vaccination, and evaluated how mRNA vaccination influenced nasal microbiota in 18 healthy participants who had received the third BNT162b.

          Results

          The nasal S-RBD IgG level correlated significantly with plasma IgG levels until 1 month and the levels were sustained for 3 months post-vaccination. In contrast, nasal S-RBD IgA induction peaked at 1 month, albeit slightly, and correlated only with plasma IgA, but the induction level decreased markedly at 3 months post-vaccination. 16 S rRNA sequencing of the nasal microbiota post-vaccination revealed not an overall change, but a decrease in certain opportunistic bacteria, mainly Fusobacterium. The decrease in these bacteria was more pronounced in those who exhibited nasal S-RBD IgA induction, and those with higher S-RBD IgA induction had lower relative amounts of potentially pathogenic bacteria such as Pseudomonas pre-vaccination. In addition, plasma and mucosal S-RBD IgG levels correlated with decreased commensal pathogens such as Finegoldia.

          Conclusions

          These findings suggest that the third dose of SARS-CoV-2 mRNA vaccination induced S-RBD antibodies in the nasal mucosa and may have stimulated mucosal immunity against opportunistic bacterial pathogens. This effect, albeit probably secondary, may be considered one of the benefits of mRNA vaccination. Furthermore, our data suggest that a cooperative function of mucosal and systemic immunity in the reduction of bacteria and provides a better understanding of the symbiotic relationship between the host and bacteria in the nasal mucosa.

          Supplementary Information

          The online version contains supplementary material available at 10.1186/s12985-023-02113-z.

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          Most cited references42

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          DADA2: High resolution sample inference from Illumina amplicon data

          We present DADA2, a software package that models and corrects Illumina-sequenced amplicon errors. DADA2 infers sample sequences exactly, without coarse-graining into OTUs, and resolves differences of as little as one nucleotide. In several mock communities DADA2 identified more real variants and output fewer spurious sequences than other methods. We applied DADA2 to vaginal samples from a cohort of pregnant women, revealing a diversity of previously undetected Lactobacillus crispatus variants.
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            The SILVA ribosomal RNA gene database project: improved data processing and web-based tools

            SILVA (from Latin silva, forest, http://www.arb-silva.de) is a comprehensive web resource for up to date, quality-controlled databases of aligned ribosomal RNA (rRNA) gene sequences from the Bacteria, Archaea and Eukaryota domains and supplementary online services. The referred database release 111 (July 2012) contains 3 194 778 small subunit and 288 717 large subunit rRNA gene sequences. Since the initial description of the project, substantial new features have been introduced, including advanced quality control procedures, an improved rRNA gene aligner, online tools for probe and primer evaluation and optimized browsing, searching and downloading on the website. Furthermore, the extensively curated SILVA taxonomy and the new non-redundant SILVA datasets provide an ideal reference for high-throughput classification of data from next-generation sequencing approaches.
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              Reproducible, interactive, scalable and extensible microbiome data science using QIIME 2

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                Author and article information

                Contributors
                mizutanitaketoshi@g.ecc.u-tokyo.ac.jp
                yotsudid@ims.u-tokyo.ac.jp
                Journal
                Virol J
                Virol J
                Virology Journal
                BioMed Central (London )
                1743-422X
                13 July 2023
                13 July 2023
                2023
                : 20
                : 146
                Affiliations
                [1 ]GRID grid.26999.3d, ISNI 0000 0001 2151 536X, Division of Infectious Diseases, Advanced Clinical Research Center, The Institute of Medical Science, , The University of Tokyo, ; 4-6-1 Shirokanedai, Minato-ku, 108-8639 Tokyo, Japan
                [2 ]GRID grid.26999.3d, ISNI 0000 0001 2151 536X, Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, , The University of Tokyo, ; 5-1-5 Kashiwanoha Kashiwa 277, 8562 Chiba, Japan
                [3 ]GRID grid.26999.3d, ISNI 0000 0001 2151 536X, Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, , The University of Tokyo, ; Tokyo, Japan
                [4 ]GRID grid.45203.30, ISNI 0000 0004 0489 0290, The Research Center for Global Viral Diseases, , National Center for Global Health and Medicine Research Institute, ; Tokyo, Japan
                [5 ]GRID grid.26999.3d, ISNI 0000 0001 2151 536X, Department of Infectious Diseases and Applied Immunology, IMSUT Hospital of Institute of Medical Science, , The University of Tokyo, ; Tokyo, Japan
                [6 ]GRID grid.26999.3d, ISNI 0000 0001 2151 536X, Department of Infectious Diseases, , The University of Tokyo, ; Tokyo, Japan
                [7 ]GRID grid.14003.36, ISNI 0000 0001 2167 3675, Influenza Research Institute, Department of Pathobiological Sciences, School of Veterinary Medicine, , University of Wisconsin–Madison, ; Madison, WI USA
                [8 ]GRID grid.26999.3d, ISNI 0000 0001 2151 536X, Pandemic Preparedness, Infection and Advanced Research Center, , The University of Tokyo, ; Tokyo, Japan
                Article
                2113
                10.1186/s12985-023-02113-z
                10339591
                a74a8624-51ad-416c-9113-1704e8e7ed51
                © The Author(s) 2023

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

                History
                : 23 March 2023
                : 3 July 2023
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/501100001691, Japan Society for the Promotion of Science;
                Award ID: 22K20926
                Award ID: 21K07314
                Award ID: 21K11592
                Funded by: The Yamaguchi Education and Scholarship Foundation (Nagaoka City, Japan)
                Funded by: FundRef http://dx.doi.org/10.13039/501100020963, Moonshot Research and Development Program;
                Award ID: JPMJMS2025
                Funded by: FundRef http://dx.doi.org/10.13039/100009619, Japan Agency for Medical Research and Development;
                Award ID: UTOPIA, 223fa627001h0001
                Award ID: JP22wm0125002 and JP223fa627001
                Categories
                Research
                Custom metadata
                © BioMed Central Ltd., part of Springer Nature 2023

                Microbiology & Virology
                sars-cov-2,covid-19,microbiota,commensal bacteria
                Microbiology & Virology
                sars-cov-2, covid-19, microbiota, commensal bacteria

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