{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,23]],"date-time":"2026-01-23T20:12:18Z","timestamp":1769199138687,"version":"3.49.0"},"reference-count":26,"publisher":"Oxford University Press (OUP)","issue":"12","license":[{"start":{"date-parts":[[2022,5,17]],"date-time":"2022-05-17T00:00:00Z","timestamp":1652745600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100019973","name":"Minist\u00e8re de l\u2019Enseignement Sup\u00e9rieur et de la Recherche","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100019973","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,12,19]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Mucosal antibodies can prevent virus entry and replication in mucosal epithelial cells and therefore virus shedding. Parenteral booster injection of a vaccine against a mucosal pathogen promotes stronger mucosal immune responses following prior mucosal infection compared with injections of a parenteral vaccine in a mucosally naive subject. We investigated whether this was also the case for the BNT162b2 coronavirus disease 2019 (COVID-19) messenger RNA vaccine.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Twenty recovered COVID-19 subjects (RCSs) and 23 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)\u2013naive subjects were vaccinated with, respectively, 1 and 2 doses of the BNT162b2 COVID-19 vaccine. Nasal epithelial lining fluid (NELF) and plasma were collected before and after vaccination and assessed for immunoglobulin G (IgG) and IgA antibody levels to Spike and for their ability to neutralize binding of Spike to angiotensin-converting enzyme-2 receptor. Blood was analyzed 1 week after vaccination for the number of Spike-specific antibody-secreting cells (ASCs) with a mucosal tropism.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>All RCSs had both nasal and blood SARS-CoV-2\u2013specific antibodies at least 90 days after initial diagnosis. In RCSs, a single dose of vaccine amplified preexisting Spike-specific IgG and IgA antibody responses in both NELF and blood against both vaccine homologous and variant strains, including Delta. These responses were associated with Spike-specific IgG and IgA ASCs with a mucosal tropism in blood. Nasal IgA and IgG antibody responses were lower in magnitude in SARS-CoV-2\u2013naive subjects after 2 vaccine doses compared with RCSs after 1 dose.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Mucosal immune response to the SARS-CoV-2 Spike protein is higher in RCSs after a single vaccine dose compared with SARS-CoV-2\u2013naive subjects after 2 doses.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/cid\/ciac378","type":"journal-article","created":{"date-parts":[[2022,5,17]],"date-time":"2022-05-17T19:20:30Z","timestamp":1652815230000},"page":"2053-2059","source":"Crossref","is-referenced-by-count":12,"title":["A Single Dose of BNT162b2 Messenger RNA Vaccine Induces Airway Immunity in Severe Acute Respiratory Syndrome Coronavirus 2 Naive and Recovered Coronavirus Disease 2019 Subjects"],"prefix":"10.1093","volume":"75","author":[{"given":"Emanuela","family":"Martinuzzi","sequence":"first","affiliation":[{"name":"Universit\u00e9 C\u00f4te d\u2019Azur, CNRS, Institut de Pharmacologie Mol\u00e9culaire et Cellulaire , Valbonne , France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jonathan","family":"Benzaquen","sequence":"additional","affiliation":[{"name":"Universit\u00e9 C\u00f4te d\u2019Azur, Centre Hospitalier Universitaire de Nice, Department of Pulmonary Medicine and Thoracic Oncology, FHU OncoAge , Nice , France"},{"name":"Universit\u00e9 C\u00f4te d\u2019Azur, CNRS, INSERM, Institute of Research on Cancer and Aging , Nice , France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Olivier","family":"Guerin","sequence":"additional","affiliation":[{"name":"Universit\u00e9 C\u00f4te d\u2019Azur, Centre Hospitalier Universitaire de Nice, P\u00f4le R\u00e9habilitation Autonomie Vieillissement , Nice , France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sylvie","family":"Leroy","sequence":"additional","affiliation":[{"name":"Universit\u00e9 C\u00f4te d\u2019Azur, CNRS, Institut de Pharmacologie Mol\u00e9culaire et Cellulaire , Valbonne , France"},{"name":"Universit\u00e9 C\u00f4te d\u2019Azur, Centre Hospitalier Universitaire de Nice, Department of Pulmonary Medicine and Thoracic Oncology, FHU OncoAge , Nice , France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas","family":"Simon","sequence":"additional","affiliation":[{"name":"Universit\u00e9 C\u00f4te d\u2019Azur, CNRS, Institut de Pharmacologie Mol\u00e9culaire et Cellulaire , Valbonne , France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marius","family":"Ilie","sequence":"additional","affiliation":[{"name":"Universit\u00e9 C\u00f4te d\u2019Azur, CNRS, INSERM, Institute of Research on Cancer and Aging , Nice , France"},{"name":"Universit\u00e9 C\u00f4te d\u2019Azur, Centre Hospitalier Universitaire de Nice, Laboratory of Clinical and Experimental Pathology , Biobank (BB-0033-00025), FHU OncoAge, Centre Nice , France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"V\u00e9ronique","family":"Hofman","sequence":"additional","affiliation":[{"name":"Universit\u00e9 C\u00f4te d\u2019Azur, CNRS, INSERM, Institute of Research on Cancer and Aging , Nice , France"},{"name":"Universit\u00e9 C\u00f4te d\u2019Azur, Centre Hospitalier Universitaire de Nice, Laboratory of Clinical and Experimental Pathology , Biobank (BB-0033-00025), FHU OncoAge, Centre Nice , France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maryline","family":"Allegra","sequence":"additional","affiliation":[{"name":"Universit\u00e9 C\u00f4te d\u2019Azur, Centre Hospitalier Universitaire de Nice, Laboratory of Clinical and Experimental Pathology , Biobank (BB-0033-00025), FHU OncoAge, Centre Nice , France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Virginie","family":"Tanga","sequence":"additional","affiliation":[{"name":"Universit\u00e9 C\u00f4te d\u2019Azur, Centre Hospitalier Universitaire de Nice, Laboratory of Clinical and Experimental Pathology , Biobank (BB-0033-00025), FHU OncoAge, Centre Nice , France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emeline","family":"Michel","sequence":"additional","affiliation":[{"name":"Universit\u00e9 C\u00f4te d\u2019Azur, Centre Hospitalier Universitaire de Nice, P\u00f4le R\u00e9habilitation Autonomie Vieillissement , Nice , France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jacques","family":"Boutros","sequence":"additional","affiliation":[{"name":"Universit\u00e9 C\u00f4te d\u2019Azur, Centre Hospitalier Universitaire de Nice, Department of Pulmonary Medicine and Thoracic Oncology, FHU OncoAge , Nice , France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Charlotte","family":"Maniel","sequence":"additional","affiliation":[{"name":"Universit\u00e9 C\u00f4te d\u2019Azur, Centre Hospitalier Universitaire de Nice, Department of Pulmonary Medicine and Thoracic Oncology, FHU OncoAge , Nice , France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antoine","family":"Sicard","sequence":"additional","affiliation":[{"name":"University Co\u0302te d\u2019Azur, Clinical Research Unit Co\u0302te d\u2019Azur , Nice , France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicolas","family":"Glaichenhaus","sequence":"additional","affiliation":[{"name":"Universit\u00e9 C\u00f4te d\u2019Azur, CNRS, Institut de Pharmacologie Mol\u00e9culaire et Cellulaire , Valbonne , France"},{"name":"University Co\u0302te d\u2019Azur, Clinical Research Unit Co\u0302te d\u2019Azur , Nice , France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cecil","family":"Czerkinsky","sequence":"additional","affiliation":[{"name":"Universit\u00e9 C\u00f4te d\u2019Azur, CNRS, Institut de Pharmacologie Mol\u00e9culaire et Cellulaire , Valbonne , France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Philippe","family":"Blancou","sequence":"additional","affiliation":[{"name":"Universit\u00e9 C\u00f4te d\u2019Azur, CNRS, Institut de Pharmacologie Mol\u00e9culaire et Cellulaire , Valbonne , France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paul","family":"Hofman","sequence":"additional","affiliation":[{"name":"Universit\u00e9 C\u00f4te d\u2019Azur, CNRS, INSERM, Institute of Research on Cancer and Aging , Nice , France"},{"name":"Universit\u00e9 C\u00f4te d\u2019Azur, Centre Hospitalier Universitaire de Nice, Laboratory of Clinical and Experimental Pathology , Biobank (BB-0033-00025), FHU OncoAge, Centre Nice , France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Charles H","family":"Marquette","sequence":"additional","affiliation":[{"name":"Universit\u00e9 C\u00f4te d\u2019Azur, Centre Hospitalier Universitaire de Nice, Department of Pulmonary Medicine and Thoracic Oncology, FHU OncoAge , Nice , France"},{"name":"Universit\u00e9 C\u00f4te d\u2019Azur, CNRS, INSERM, Institute of Research on Cancer and Aging , Nice , France"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2022,5,17]]},"reference":[{"key":"2022121911374589700_ciac378-B1","doi-asserted-by":"crossref","first-page":"e92","DOI":"10.1056\/NEJMc2113090","article-title":"Effectiveness of Covid-19 vaccines against the B.1.617.2 (Delta) variant","volume":"385","author":"Linsenmeyer","year":"2021","journal-title":"N Engl J Med"},{"key":"2022121911374589700_ciac378-B2","doi-asserted-by":"crossref","first-page":"e92","DOI":"10.1056\/NEJMc2113090","article-title":"Effectiveness of Covid-19 vaccines against the B.1.617.2 (Delta) variant","volume":"385","author":"Emani","year":"2021","journal-title":"N Engl J Med"},{"key":"2022121911374589700_ciac378-B3","doi-asserted-by":"crossref","first-page":"e92","DOI":"10.1056\/NEJMc2113090","article-title":"Effectiveness of Covid-19 vaccines against the B.1.617.2 (Delta) variant","volume":"385","author":"Torgovnick","year":"2021","journal-title":"N Engl J Med"},{"key":"2022121911374589700_ciac378-B4","doi-asserted-by":"crossref","first-page":"1718","DOI":"10.1056\/NEJMc2106757","article-title":"Effect of vaccination on transmission of SARS-CoV-2","volume":"385","author":"Shah","year":"2021","journal-title":"N Engl J Med"},{"key":"2022121911374589700_ciac378-B5","doi-asserted-by":"crossref","first-page":"759","DOI":"10.1056\/NEJMc2107717","article-title":"Effect of vaccination on household transmission of SARS-CoV-2 in England","volume":"385","author":"Harris","year":"2021","journal-title":"N Engl J Med"},{"key":"2022121911374589700_ciac378-B6","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1016\/S1473-3099(21)00648-4","article-title":"Community transmission and viral load kinetics of the SARS-CoV-2 delta (B.1.617.2) variant in vaccinated and unvaccinated individuals in the UK: a prospective, longitudinal, cohort study","volume":"22","author":"Singanayagam","year":"2021","journal-title":"Lancet Infect Dis"},{"key":"2022121911374589700_ciac378-B7","doi-asserted-by":"crossref","first-page":"2012","DOI":"10.1038\/s41591-021-01488-2","article-title":"Convalescent plasma for hospitalized patients with COVID-19: an open-label, randomized controlled trial","volume":"27","author":"Begin","year":"2021","journal-title":"Nat Med"},{"key":"2022121911374589700_ciac378-B8","doi-asserted-by":"crossref","first-page":"185","DOI":"10.3389\/fimmu.2013.00185","article-title":"Multi-faceted functions of secretory IgA at mucosal surfaces","volume":"4","author":"Corthesy","year":"2013","journal-title":"Front Immunol"},{"key":"2022121911374589700_ciac378-B9","doi-asserted-by":"crossref","first-page":"eabd2223","DOI":"10.1126\/scitranslmed.abd2223","article-title":"IgA dominates the early neutralizing antibody response to SARS-CoV-2","volume":"13","author":"Sterlin","year":"2021","journal-title":"Sci Transl Med"},{"key":"2022121911374589700_ciac378-B10","doi-asserted-by":"crossref","first-page":"e2107148118","DOI":"10.1073\/pnas.2107148118","article-title":"Increased in vitro neutralizing activity of SARS-CoV-2 IgA1 dimers compared to monomers and IgG","volume":"118","author":"Sun","year":"2021","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2022121911374589700_ciac378-B111","doi-asserted-by":"crossref","first-page":"101735","DOI":"10.1016\/j.isci.2020.101735","article-title":"Robust and specific secretory IgA against SARS-CoV-2 detected in human milk","volume":"23","author":"Fox","year":"2020","journal-title":"iScience"},{"key":"2022121911374589700_ciac378-B112","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1111\/imm.13349","article-title":"Development of a high-sensitivity ELISA detecting IgG, IgA and IgM antibodies to the SARS-CoV-2 spike glycoprotein in serum and saliva","volume":"164","author":"Faustini","year":"2021","journal-title":"Immunology"},{"key":"2022121911374589700_ciac378-B113","doi-asserted-by":"crossref","first-page":"595343","DOI":"10.3389\/fimmu.2021.595343","article-title":"In nasal mucosal secretions, distinct IFN and IgA responses are found in severe and mild SARS-CoV-2 infection","volume":"12","author":"Dos Santos","year":"2021","journal-title":"Front Immunol"},{"key":"2022121911374589700_ciac378-B114","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1038\/s41577-021-00583-2","article-title":"Mucosal vaccines - fortifying the frontiers","volume":"22","author":"Lavelle","year":"2022","journal-title":"Nat Rev Immunol"},{"key":"2022121911374589700_ciac378-B14","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1038\/s41577-021-00599-8","article-title":"Publisher correction: Mucosal vaccines - fortifying the frontiers","volume":"22","author":"Lavelle","year":"2021","journal-title":"Nat Rev Immunol"},{"key":"2022121911374589700_ciac378-B12","doi-asserted-by":"crossref","first-page":"e0146010","DOI":"10.1371\/journal.pone.0146010","article-title":"Human circulating antibody-producing B cell as a predictive measure of mucosal immunity to poliovirus","volume":"11","author":"Dey","year":"2016","journal-title":"PLoS One"},{"key":"2022121911374589700_ciac378-B13","author":"Authority","year":"2021"},{"key":"2022121911374589700_ciac378-B15","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1089\/bio.2020.0055","article-title":"Establishment of a collection of blood-derived products from COVID-19 patients for translational research: Experience of the LPCE biobank (Nice, France)","volume":"18","author":"Tanga","year":"2020","journal-title":"Biopreserv Biobank"},{"key":"2022121911374589700_ciac378-B16","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1007\/s00405-003-0691-y","article-title":"Collection of nasal secretions for immunological analysis","volume":"261","author":"Watelet","year":"2004","journal-title":"Eur Arch Otorhinolaryngol"},{"key":"2022121911374589700_ciac378-B17","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1038\/s41586-021-03681-2","article-title":"Immunogenicity of Ad26.COV2.S vaccine against SARS-CoV-2 variants in humans","volume":"596","author":"Alter","year":"2021","journal-title":"Nature"},{"key":"2022121911374589700_ciac378-B18","doi-asserted-by":"crossref","first-page":"e888","DOI":"10.1093\/cid\/ciab938","article-title":"A higher antibody response is generated with a 6- to 7-week (vs standard) severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine dosing interval","volume":"75","author":"Grunau","year":"2022","journal-title":"Clin Infect Dis"},{"key":"2022121911374589700_ciac378-B19","doi-asserted-by":"crossref","first-page":"1073","DOI":"10.1038\/nprot.2013.058","article-title":"Enzyme-linked immunospot assays for direct ex vivo measurement of vaccine-induced human humoral immune responses in blood","volume":"8","author":"Saletti","year":"2013","journal-title":"Nat Protoc"},{"key":"2022121911374589700_ciac378-B20","doi-asserted-by":"crossref","first-page":"5621","DOI":"10.1038\/s41467-021-25949-x","article-title":"SARS-CoV-2 mucosal antibody development and persistence and their relation to viral load and COVID-19 symptoms","volume":"12","author":"Froberg","year":"2021","journal-title":"Nat Commun"},{"key":"2022121911374589700_ciac378-B21","doi-asserted-by":"crossref","first-page":"1499","DOI":"10.3390\/vaccines9121499","article-title":"Nasal and salivary mucosal humoral immune response elicited by mRNA BNT162b2 COVID-19 vaccine compared to SARS-CoV-2 natural infection","volume":"9","author":"Guerrieri","year":"2021","journal-title":"Vaccines (Basel)"},{"key":"2022121911374589700_ciac378-B22","doi-asserted-by":"crossref","first-page":"222","DOI":"10.3389\/fimmu.2013.00222","article-title":"Secretory IgA: designed for anti-microbial defense","volume":"4","author":"Brandtzaeg","year":"2013","journal-title":"Front Immunol"},{"key":"2022121911374589700_ciac378-B23","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1038\/s41541-021-00405-5","article-title":"Mucosal vaccination induces protection against SARS-CoV-2 in the absence of detectable neutralizing antibodies","volume":"6","author":"Zhong","year":"2021","journal-title":"NPJ Vaccines"}],"container-title":["Clinical Infectious Diseases"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/cid\/advance-article-pdf\/doi\/10.1093\/cid\/ciac378\/44329420\/ciac378.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/cid\/article-pdf\/75\/12\/2053\/48162596\/ciac378.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/cid\/article-pdf\/75\/12\/2053\/48162596\/ciac378.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,19]],"date-time":"2022-12-19T11:54:35Z","timestamp":1671450875000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/cid\/article\/75\/12\/2053\/6586846"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,5,17]]},"references-count":26,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2022,5,17]]},"published-print":{"date-parts":[[2022,12,19]]}},"URL":"https:\/\/doi.org\/10.1093\/cid\/ciac378","relation":{},"ISSN":["1058-4838","1537-6591"],"issn-type":[{"value":"1058-4838","type":"print"},{"value":"1537-6591","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2022,12,15]]},"published":{"date-parts":[[2022,5,17]]}}}