{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T06:47:45Z","timestamp":1777963665627,"version":"3.51.4"},"reference-count":23,"publisher":"Oxford University Press (OUP)","issue":"4","funder":[{"name":"Infectious Diseases Clinical Research Consortium"},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["UM1AI48372"],"award-info":[{"award-number":["UM1AI48372"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["UM1AI148373"],"award-info":[{"award-number":["UM1AI148373"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["UM1AI148450"],"award-info":[{"award-number":["UM1AI148450"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["UM1AI148452"],"award-info":[{"award-number":["UM1AI148452"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["UM1AI148573"],"award-info":[{"award-number":["UM1AI148573"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["UM1AI148574"],"award-info":[{"award-number":["UM1AI148574"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["UM1AI148575"],"award-info":[{"award-number":["UM1AI148575"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["UM1AI148576"],"award-info":[{"award-number":["UM1AI148576"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["UM1AI148684"],"award-info":[{"award-number":["UM1AI148684"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["UM1 AI148689)"],"award-info":[{"award-number":["UM1 AI148689)"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"name":"NIAID Collaborative Influenza Vaccine Innovation Centers","award":["75N93019C00050)"],"award-info":[{"award-number":["75N93019C00050)"]}]},{"DOI":"10.13039\/100016820","name":"National Institutes of Health Vaccine Research Center","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100016820","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,10,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Mucosal immunity plays a critical role in preventing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and replication. Understanding the capacity of coronavirus disease 2019 (COVID-19) vaccines to elicit both mucosal and systemic antibodies could help optimize vaccination strategies.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>We conducted an open-label, phase 1\/2 adaptive-design clinical trial to evaluate the safety and immunogenicity of COVID-19 immunizations. Healthy adults received 2 priming doses of mRNA-1273, a booster dose of mRNA-1273, and a second booster of bivalent (WA-1 and BA.4\/BA.5) mRNA-1273.222. Adverse event data were collected. Serum and mucosal immunity were evaluated.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>One hundred six persons were enrolled. Thirty received all 4 study-related vaccine doses. All vaccines were well tolerated, with injection site pain, malaise, myalgias, and headache being the most frequently reported symptoms. Among those who received a second booster, 24 of 30 (80%) had serological evidence of SARS-CoV-2 infection. Following the second booster, increases in geometric mean binding and pseudovirus neutralization antibody titers to the ancestral strain and BA.1 and BA.5 variants were observed. Increases in mucosal immunoglobulin G and immunoglobulin A (IgA) antibodies in nasal and salivary samples were observed in both previously infected and infection-naive participants, although prior infection markedly boosted virus-specific mucosal IgA responses.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>The mRNA-1273.222 booster vaccine was safe and immunogenic and induced mucosal antibody responses in previously infected and infection-naive persons.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Clinical Trials Registration<\/jats:title>\n                  <jats:p>NCT04889209.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/infdis\/jiaf176","type":"journal-article","created":{"date-parts":[[2025,4,29]],"date-time":"2025-04-29T09:01:39Z","timestamp":1745917299000},"page":"971-981","source":"Crossref","is-referenced-by-count":4,"title":["Mucosal and Systemic Antibody Responses After Boosting With a Bivalent Messenger RNA Severe Acute Respiratory Syndrome Coronavirus 2 Vaccine"],"prefix":"10.1093","volume":"232","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9989-6772","authenticated-orcid":false,"given":"Robert L","family":"Atmar","sequence":"first","affiliation":[{"name":"Departments of Medicine and Molecular Virology and Microbiology, Baylor College of Medicine , Houston, Texas ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4966-0830","authenticated-orcid":false,"given":"Kirsten E","family":"Lyke","sequence":"additional","affiliation":[{"name":"Center for Vaccine Development and Global Health, University of Maryland School of Medicine , Baltimore, Maryland ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5641-3934","authenticated-orcid":false,"given":"Christine M","family":"Posavad","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathology, University of Washington , Seattle, Washington ,","place":["USA"]},{"name":"Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center , Seattle, Washington ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2574-0542","authenticated-orcid":false,"given":"Meagan E","family":"Deming","sequence":"additional","affiliation":[{"name":"Center for Vaccine Development and Global Health, University of Maryland School of Medicine , Baltimore, Maryland ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7635-6172","authenticated-orcid":false,"given":"Rebecca C","family":"Brady","sequence":"additional","affiliation":[{"name":"Cincinnati Children's Hospital Medical Center, Division of Infectious Diseases, University of Cincinnati College of Medicine , Cincinnati, Ohio ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5652-7432","authenticated-orcid":false,"given":"David","family":"Dobrzynski","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Department of Medicine, University of Rochester , Rochester, New York ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Srilatha","family":"Edupuganti","sequence":"additional","affiliation":[{"name":"Department of Medicine, Emory University School of Medicine , Atlanta, Georgia ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mark J","family":"Mulligan","sequence":"additional","affiliation":[{"name":"New York University Langone Vaccine Center and Division of Infectious Diseases and Immunology, Department of Medicine, New York University Grossman School of Medicine , New York, New York ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9659-1217","authenticated-orcid":false,"given":"Richard E","family":"Rupp","sequence":"additional","affiliation":[{"name":"Sealy Institute for Vaccine Sciences, University of Texas Medical Branch , Galveston, Texas ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8439-0592","authenticated-orcid":false,"given":"Christina A","family":"Rostad","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Center for Childhood Infections and Vaccines, Emory University School of Medicine and Children's Healthcare of Atlanta , Atlanta, Georgia ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1785-0218","authenticated-orcid":false,"given":"Lisa A","family":"Jackson","sequence":"additional","affiliation":[{"name":"Kaiser Permanente Washington Health Research Institute , Seattle, Washington ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9456-1770","authenticated-orcid":false,"given":"Judith M","family":"Martin","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Pittsburgh School of Medicine , Pittsburgh, Pennsylvania ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-6536-3218","authenticated-orcid":false,"given":"Mallory C","family":"Shriver","sequence":"additional","affiliation":[{"name":"Center for Vaccine Development and Global Health, University of Maryland School of Medicine , Baltimore, Maryland ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kumaravel","family":"Rajakumar","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Pittsburgh School of Medicine , Pittsburgh, Pennsylvania ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rhea N","family":"Coler","sequence":"additional","affiliation":[{"name":"Seattle Children's Research Institute , Seattle, Washington ,","place":["USA"]},{"name":"Department of Pediatrics, University of Washington School of Medicine , Seattle, Washington ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hana M","family":"El Sahly","sequence":"additional","affiliation":[{"name":"Departments of Medicine and Molecular Virology and Microbiology, Baylor College of Medicine , Houston, Texas ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4103-1666","authenticated-orcid":false,"given":"Angelica C","family":"Kottkamp","sequence":"additional","affiliation":[{"name":"New York University Langone Vaccine Center and Division of Infectious Diseases and Immunology, Department of Medicine, New York University Grossman School of Medicine , New York, New York ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7742-5352","authenticated-orcid":false,"given":"Angela R","family":"Branche","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Department of Medicine, University of Rochester , Rochester, New York ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2336-526X","authenticated-orcid":false,"given":"Robert 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Bethesda, Maryland ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0856-6319","authenticated-orcid":false,"given":"David C","family":"Montefiori","sequence":"additional","affiliation":[{"name":"Duke Human Vaccine Institute, Duke University Medical Center , Durham, North Carolina ,","place":["USA"]},{"name":"Department of Surgery, Duke University Medical Center , Durham, North Carolina ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3064-2947","authenticated-orcid":false,"given":"Amanda","family":"Eaton","sequence":"additional","affiliation":[{"name":"Department of Surgery, Duke University Medical Center , Durham, North Carolina ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9480-2714","authenticated-orcid":false,"given":"Kathleen 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,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0894-4009","authenticated-orcid":false,"given":"Marcela","family":"Pasetti","sequence":"additional","affiliation":[{"name":"Center for Vaccine Development and Global Health, University of Maryland School of Medicine , Baltimore, Maryland ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4452-141X","authenticated-orcid":false,"given":"Paul C","family":"Roberts","sequence":"additional","affiliation":[{"name":"Division of Microbiology and Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health , Bethesda, Maryland 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