{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T20:48:33Z","timestamp":1791492513750,"version":"4.3.4"},"reference-count":55,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"798","content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Transl. Med."],"published-print":{"date-parts":[[2025,5,14]]},"abstract":"<jats:p>\n                    There are currently no licensed vaccines for norovirus, a leading cause of epidemic and endemic gastroenteritis worldwide. Clinical advancement of promising vaccine candidates from phase 2 studies to phase 3 field trials has been hampered by the lack of robust immunological correlates of protection. Here, we conducted a phase 2b randomized, placebo-controlled vaccination and challenge study to assess the safety, efficacy, immunogenicity, and correlates of protection of VXA-G1.1-NN, an oral tablet norovirus vaccine. VXA-G1.1-NN was safe and well tolerated, conferred protection against norovirus GI.1 challenge, and reduced viral shedding in stool and emesis. Norovirus VP1-specific serum immunoglobulin A (IgA), IgG, and functional blocking antibody titers increased substantially after oral vaccination. Moreover, oral immunization stimulated VP1-specific IgA antibodies in nasal lining fluid, saliva, and fecal samples. Serum and mucosal antibody responses 7 days after vaccination were correlated with the induction of antibody-secreting, \u03b14\u03b27\n                    <jats:sup>+<\/jats:sup>\n                    mucosal-homing B cells. Machine learning analyses of vaccine-stimulated immune components identified serum functional blocking antibody and fecal IgA as robust correlates of protection. These results demonstrate the potential of VXA-G1.1-NN as a safe and effective oral norovirus vaccine and reveal critical immunological features underpinning vaccine efficacy.\n                  <\/jats:p>","DOI":"10.1126\/scitranslmed.adh9906","type":"journal-article","created":{"date-parts":[[2025,5,14]],"date-time":"2025-05-14T13:58:37Z","timestamp":1747231117000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":21,"title":["An oral norovirus vaccine generates mucosal immunity and reduces viral shedding in a phase 2 placebo-controlled challenge study"],"prefix":"10.1126","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3478-8751","authenticated-orcid":true,"given":"Becca A.","family":"Flitter","sequence":"first","affiliation":[{"name":"Vaxart Inc., South San Francisco, CA 94080, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joshua","family":"Gillard","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan N.","family":"Greco","sequence":"additional","affiliation":[{"name":"Vaxart Inc., South San Francisco, CA 94080, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-6229-6592","authenticated-orcid":true,"given":"Maria D.","family":"Apkarian","sequence":"additional","affiliation":[{"name":"Vaxart Inc., South San Francisco, CA 94080, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-7055-1215","authenticated-orcid":true,"given":"Nick P.","family":"D\u2019Amato","sequence":"additional","affiliation":[{"name":"Vaxart Inc., South San Francisco, CA 94080, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-2722-6786","authenticated-orcid":true,"given":"Lam Quynh","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Vaxart Inc., South San Francisco, CA 94080, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena D.","family":"Neuhaus","sequence":"additional","affiliation":[{"name":"Vaxart Inc., South San Francisco, CA 94080, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Darreann Carmela M.","family":"Hailey","sequence":"additional","affiliation":[{"name":"Vaxart Inc., South San Francisco, CA 94080, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0894-4009","authenticated-orcid":true,"given":"Marcela F.","family":"Pasetti","sequence":"additional","affiliation":[{"name":"Center for Vaccine Development, University of Maryland Baltimore School of Medicine, Baltimore, MD 21201, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-6536-3218","authenticated-orcid":true,"given":"Mallory","family":"Shriver","sequence":"additional","affiliation":[{"name":"Center for Vaccine Development, University of Maryland Baltimore School of Medicine, Baltimore, MD 21201, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-8190-5333","authenticated-orcid":true,"given":"Christina","family":"Quigley","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Cincinnati Children\u2019s Hospital Medical Center, Cincinnati, OH 45229, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2336-526X","authenticated-orcid":true,"suffix":"Jr.","given":"Robert W.","family":"Frenck","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Cincinnati Children\u2019s Hospital Medical Center, Cincinnati, OH 45229, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9567-0522","authenticated-orcid":true,"given":"Lisa C.","family":"Lindesmith","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, University of North Carolina, Chapel Hill, NC 27599, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6827-8701","authenticated-orcid":true,"given":"Ralph S.","family":"Baric","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, University of North Carolina, Chapel Hill, NC 27599, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lee-Jen","family":"Wei","sequence":"additional","affiliation":[{"name":"Harvard T.H. Chan School of Public Health, Harvard University, Boston, MA 02115, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6233-225X","authenticated-orcid":true,"given":"Sean N.","family":"Tucker","sequence":"additional","affiliation":[{"name":"Vaxart Inc., South San Francisco, CA 94080, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-2880-8009","authenticated-orcid":true,"given":"James F.","family":"Cummings","sequence":"additional","affiliation":[{"name":"Vaxart Inc., South San Francisco, CA 94080, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(14)70767-4"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra0804575"},{"key":"e_1_3_2_4_2","unstructured":"US Centers of Disease Control \u201cUpdated norovirus outbreak management and disease prevention guidelines\u201d MMWR Recomm. 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Wickham \u201cTidymodels: A collection of packages for modeling and machine learning using tidyverse principles\u201d (2020); https:\/\/cran.r-project.org\/web\/packages\/tidymodels\/citation.html; www.tidymodels.org\/."},{"key":"e_1_3_2_56_2","doi-asserted-by":"publisher","DOI":"10.18637\/jss.v033.i01"}],"container-title":["Science Translational Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.science.org\/doi\/pdf\/10.1126\/scitranslmed.adh9906","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,5,14]],"date-time":"2025-05-14T13:58:58Z","timestamp":1747231138000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.science.org\/doi\/10.1126\/scitranslmed.adh9906"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5,14]]},"references-count":55,"journal-issue":{"issue":"798","published-print":{"date-parts":[[2025,5,14]]}},"alternative-id":["10.1126\/scitranslmed.adh9906"],"URL":"https:\/\/doi.org\/10.1126\/scitranslmed.adh9906","relation":{},"ISSN":["1946-6234","1946-6242"],"issn-type":[{"value":"1946-6234","type":"print"},{"value":"1946-6242","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,5,14]]},"assertion":[{"value":"2024-11-27","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-04-17","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-05-14","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"eadh9906"}}