{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T01:52:15Z","timestamp":1785894735752,"version":"3.56.0"},"reference-count":57,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2024,3,1]],"date-time":"2024-03-01T00:00:00Z","timestamp":1709251200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Bill &amp; Melinda Gates Foundation","award":["INV-020846"],"award-info":[{"award-number":["INV-020846"]}]},{"name":"Bill &amp; Melinda Gates Foundation","award":["INV-027499"],"award-info":[{"award-number":["INV-027499"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Vaccines"],"abstract":"<jats:p>Human rotavirus (HRV) is still a leading cause of severe dehydrating gastroenteritis globally, particularly in infants and children. Previously, we demonstrated the immunogenicity of mRNA-based HRV vaccine candidates expressing the viral spike protein VP8* in rodent models. In the present study, we assessed the immunogenicity and protective efficacy of two mRNA-based HRV trivalent vaccine candidates, encoding VP8* of the genotypes P[8], P[6], or P[4], in the gnotobiotic (Gn) pig model of Wa (G1P[8]) HRV infection and diarrhea. Vaccines either encoded VP8* alone fused to the universal T-cell epitope P2 (P2-VP8*) or expressed P2-VP8* as a fusion protein with lumazine synthase (LS-P2-VP8*) to allow the formation and secretion of protein particles that present VP8* on their surface. Gn pigs were randomly assigned into groups and immunized three times with either P2-VP8* (30 \u00b5g) or LS-P2-VP8* (30 \u00b5g or 12 \u00b5g). A trivalent alum-adjuvanted P2-VP8* protein vaccine or an LNP-formulated irrelevant mRNA vaccine served as the positive and negative control, respectively. Upon challenge with virulent Wa HRV, a significantly shortened duration and decreased severity of diarrhea and significant protection from virus shedding was induced by both mRNA vaccine candidates compared to the negative control. Both LS-P2-VP8* doses induced significantly higher VP8*-specific IgG antibody titers in the serum after immunizations than the negative as well as the protein control. The P[8] VP8*-specific IgG antibody-secreting cells in the ileum, spleen, and blood seven days post-challenge, as well as VP8*-specific IFN-\u03b3-producing T-cell numbers increased in all three mRNA-vaccinated pig groups compared to the negative control. Overall, there was a clear tendency towards improved responses in LS-P2-VP8* compared to the P2-VP8*mRNA vaccine. The demonstrated strong humoral immune responses, priming for effector T cells, and the significant reduction of viral shedding and duration of diarrhea in Gn pigs provide a promising proof of concept and may provide guidance for the further development of mRNA-based rotavirus vaccines.<\/jats:p>","DOI":"10.3390\/vaccines12030260","type":"journal-article","created":{"date-parts":[[2024,3,1]],"date-time":"2024-03-01T03:31:23Z","timestamp":1709263883000},"page":"260","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["mRNA-Based Vaccines Are Highly Immunogenic and Confer Protection in the Gnotobiotic Pig Model of Human Rotavirus Diarrhea"],"prefix":"10.3390","volume":"12","author":[{"given":"Casey","family":"Hensley","sequence":"first","affiliation":[{"name":"Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Tech, Blacksburg, VA 24060, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandro","family":"Roier","sequence":"additional","affiliation":[{"name":"CureVac SE, 72076 T\u00fcbingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peng","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Tech, Blacksburg, VA 24060, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sofia","family":"Schnur","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Tech, Blacksburg, VA 24060, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charlotte","family":"Nyblade","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia 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and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA 98109, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruizhe","family":"Wu","sequence":"additional","affiliation":[{"name":"Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA 98109, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Celia","family":"Mahoney","sequence":"additional","affiliation":[{"name":"Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA 98109, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monica M.","family":"McNeal","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Cincinnati College of Medicine, and Division of Infectious Diseases, Cincinnati Children\u2019s Hospital Medical Center, Cincinnati, OH 45229, 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