{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,27]],"date-time":"2026-01-27T11:21:18Z","timestamp":1769512878836,"version":"3.49.0"},"reference-count":21,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2025,1,17]],"date-time":"2025-01-17T00:00:00Z","timestamp":1737072000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Takeda Vaccines, Inc."},{"name":"HilleVax, Inc."}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Vaccines"],"abstract":"<jats:p>Background: Major global economic and health burdens due to norovirus gastroenteritis could be addressed by an effective vaccine. Methods: In this study, 428 adult recipients of various compositions of the norovirus vaccine candidate, HIL-214, were followed for 5 years, to assess immune responses to its virus-like particle antigens, GI.1 and GII.4c. Serum antibodies and peripheral-blood antibody-secreting cells (ASCs) were measured. This report focuses on the single-dose 15\/50 (\u00b5g GI.1\/GII.4c) composition, which had been selected for further clinical development. Results: For single-dose 15\/50 recipients (N = 105), GI.1-specific and GII.4c-specific histoblood-group antigen-blocking (HBGA) antibodies appeared to have persisted to 5 years, waning from a peak at 4 to 8 weeks, and plateauing above baseline after 3 years. From 3 to 5 years, GI.1-specific GMTs ranged between 53 (95%CI, 40\u201371) and 60 (95%CI, 46\u201377; N = 69\u201397) and were approximately 2-fold above the baseline GMT (24 (95%CI, 20\u201328); N = 105). GII.4c-specific GMTs ranged between 103 (95%CI, 77\u2013138) and 114 (95%CI, 86\u2013152; N = 70\u201397) and were above baseline, but by less than 2-fold (70 (95%CI, 53\u201392); N = 105). Similar kinetics were observed for pan-Ig titers and ASCs in a subset. Similar kinetics were also observed for HBGA and pan-Ig titers in recipients of other 15\/50 dosages. Conclusions: Immune responses to HIL-214 in adults appear to persist for five years.<\/jats:p>","DOI":"10.3390\/vaccines13010082","type":"journal-article","created":{"date-parts":[[2025,1,21]],"date-time":"2025-01-21T06:53:32Z","timestamp":1737442412000},"page":"82","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Persistence of the Immune Response to an Intramuscular Bivalent (GI.1\/GII.4) Norovirus Vaccine in Adults"],"prefix":"10.3390","volume":"13","author":[{"given":"Geert","family":"Leroux-Roels","sequence":"first","affiliation":[{"name":"Center for Vaccinology (CEVAC), Ghent University and University Hospital, 9000 Ghent, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9989-6772","authenticated-orcid":false,"given":"Robert L.","family":"Atmar","sequence":"additional","affiliation":[{"name":"Departments of Medicine and Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX 77030, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-1268-5750","authenticated-orcid":false,"given":"Jakob P.","family":"Cramer","sequence":"additional","affiliation":[{"name":"Clinical Development, Takeda Pharmaceuticals International AG, Farman Strasse 11, Opfikon, 8152 Zurich, Switzerland"},{"name":"Clinical Development, Coalition for Epidemic Preparedness Innovations (CEPI), Gibbs Building, 215 Euston Road, London NW1 2BE, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-5254-6396","authenticated-orcid":false,"given":"Ian","family":"Escudero","sequence":"additional","affiliation":[{"name":"Clinical Development, Takeda Pharmaceuticals International AG, Farman Strasse 11, Opfikon, 8152 Zurich, Switzerland"},{"name":"Clinical Development, Takeda Vaccines, 75 Sidney St., Cambridge, MA 02139, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Astrid","family":"Borkowski","sequence":"additional","affiliation":[{"name":"Clinical Development, Takeda Pharmaceuticals International AG, Farman Strasse 11, Opfikon, 8152 Zurich, Switzerland"},{"name":"HilleVax AG, Boulevard Lilienthal 42, Opfikon, 8152 Zurich, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,1,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1224","DOI":"10.3201\/eid1408.071114","article-title":"Systematic literature review of role of noroviruses in sporadic gastroenteritis","volume":"14","author":"Patel","year":"2008","journal-title":"Emerg. Infect. Dis."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Zhang, M., Fu, M., and Hu, Q. (2021). Advances in Human Norovirus Vaccine Research. Vaccines, 9.","DOI":"10.3390\/vaccines9070732"},{"key":"ref_3","first-page":"185","article-title":"Molecular epidemiology of noroviruses associated with acute sporadic gastroenteritis in children: Global distribution of genogroups, genotypes and GII.4 variants","volume":"56","author":"Trainor","year":"2013","journal-title":"J. Clin. Virol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"3580","DOI":"10.1016\/j.vaccine.2012.03.050","article-title":"Immunogenicity and specificity of norovirus Consensus GII.4 virus-like particles in monovalent and bivalent vaccine formulations","volume":"30","author":"Parra","year":"2012","journal-title":"Vaccine"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Lindesmith, L.C., Ferris, M.T., Mullan, C.W., Ferreira, J., Debbink, K., Swanstrom, J., Richardson, C., Goodwin, R.R., Baehner, F., and Mendelman, P.M. (2015). Broad blockade antibody responses in human volunteers after immunization with a multivalent norovirus VLP candidate vaccine: Immunological analyses from a phase I clinical trial. PLoS Med., 12.","DOI":"10.1371\/journal.pmed.1001807"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"410","DOI":"10.1093\/infdis\/jiy529","article-title":"An Exploratory Study of the Salivary Immunoglobulin A Responses to 1 Dose of a Norovirus Virus-Like Particle Candidate Vaccine in Healthy Adults","volume":"219","author":"Atmar","year":"2019","journal-title":"J. Infect. Dis."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1093\/infdis\/jix572","article-title":"Safety and Immunogenicity of Different Formulations of Norovirus Vaccine Candidate in Healthy Adults: A Randomized, Controlled, Double-Blind Clinical Trial","volume":"217","author":"Cramer","year":"2018","journal-title":"J. Infect. Dis."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"5842","DOI":"10.1016\/j.vaccine.2020.06.011","article-title":"A phase 2 study of the bivalent VLP norovirus vaccine candidate in older adults; impact of MPL adjuvant or a second dose","volume":"38","author":"Treanor","year":"2020","journal-title":"Vaccine"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"6442","DOI":"10.1016\/j.vaccine.2020.07.069","article-title":"Efficacy of an intramuscular bivalent norovirus GI.1\/GII.4 virus-like particle vaccine candidate in healthy US adults","volume":"38","author":"Sherwood","year":"2020","journal-title":"Vaccine"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1212","DOI":"10.1086\/656364","article-title":"Serological correlate of protection against norovirus-induced gastroenteritis","volume":"202","author":"Reeck","year":"2010","journal-title":"J. Infect. Dis."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1387","DOI":"10.1126\/science.aaf5211","article-title":"Replication of human noroviruses in stem cell-derived human enteroids","volume":"353","author":"Ettayebi","year":"2016","journal-title":"Science"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1016\/j.jim.2003.12.015","article-title":"Tracking human antigen-specific memory B cells: A sensitive and generalized ELISPOT system","volume":"286","author":"Crotty","year":"2004","journal-title":"J. Immunol. Methods"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1260","DOI":"10.3201\/eid1908.130472","article-title":"Duration of immunity to norovirus gastroenteritis","volume":"19","author":"Simmons","year":"2013","journal-title":"Emerg. Infect. Dis."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"7097","DOI":"10.1016\/j.vaccine.2012.09.040","article-title":"The potential economic value of a human norovirus vaccine for the United States","volume":"30","author":"Bartsch","year":"2012","journal-title":"Vaccine"},{"key":"ref_15","unstructured":"CDC (2024, April 22). Norovirus Burden and Trends, Available online: https:\/\/www.cdc.gov\/norovirus\/burden.html."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1111\/imr.13089","article-title":"Immunological memory to SARS-CoV-2 infection and COVID-19 vaccines","volume":"310","author":"Sette","year":"2022","journal-title":"Immunol. Rev."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Lindesmith, L.C., Boshier, F.A.T., Brewer-Jensen, P.D., Roy, S., Costantini, V., Mallory, M.L., Zweigart, M., May, S.R., Conrad, H., and O\u2019Reilly, K.M. (2022). Immune Imprinting Drives Human Norovirus Potential for Global Spread. mBio, 13.","DOI":"10.1128\/mbio.01861-22"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Nordgren, J., and Svensson, L. (2019). Genetic Susceptibility to Human Norovirus Infection: An Update. Viruses, 11.","DOI":"10.3390\/v11030226"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"e02202-19","DOI":"10.1128\/mBio.02202-19","article-title":"Population Genomics of GII.4 Noroviruses Reveal Complex Diversification and New Antigenic Sites Involved in the Emergence of Pandemic Strains","volume":"10","author":"Tohma","year":"2019","journal-title":"mBio"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"00251-20","DOI":"10.1128\/mBio.00251-20","article-title":"Genetic Manipulation of Human Intestinal Enteroids Demonstrates the Necessity of a Functional Fucosyltransferase 2 Gene for Secretor-Dependent Human Norovirus Infection","volume":"11","author":"Haga","year":"2020","journal-title":"mBio"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1402","DOI":"10.1093\/infdis\/jiad401","article-title":"A Bivalent Human Norovirus Vaccine Induces Homotypic and Heterotypic Neutralizing Antibodies","volume":"229","author":"Atmar","year":"2024","journal-title":"J. Infect. Dis."}],"container-title":["Vaccines"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-393X\/13\/1\/82\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T10:30:46Z","timestamp":1759919446000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-393X\/13\/1\/82"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1,17]]},"references-count":21,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,1]]}},"alternative-id":["vaccines13010082"],"URL":"https:\/\/doi.org\/10.3390\/vaccines13010082","relation":{},"ISSN":["2076-393X"],"issn-type":[{"value":"2076-393X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,1,17]]}}}