{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T09:01:54Z","timestamp":1767862914749,"version":"3.49.0"},"reference-count":59,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2021,7,1]],"date-time":"2021-07-01T00:00:00Z","timestamp":1625097600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01AI089634"],"award-info":[{"award-number":["R01AI089634"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pathogens"],"abstract":"<jats:p>Noroviruses (NoVs) are a leading cause of acute gastroenteritis worldwide. P particles are a potential vaccine candidate against NoV. Simvastatin is a cholesterol-reducing drug that is known to increase NoV infectivity. In this study, we examined simvastatin\u2019s effects on P particle-induced protective efficacy and T-cell immunogenicity using the gnotobiotic pig model of human NoV infection and diarrhea. Pigs were intranasally inoculated with three doses (100 \u00b5g\/dose) of GII.4\/VA387-derived P particles together with monophosphoryl lipid A and chitosan adjuvants. Simvastatin-fed pigs received 8 mg\/day orally for 11 days prior to challenge. A subset of pigs was orally challenged with 10 ID50 of a NoV GII.4\/2006b variant at post-inoculation day (PID) 28 and monitored for 7 days post-challenge. Intestinal and systemic T cell responses were determined pre- and postchallenge. Simvastatin abolished the P particle\u2019s protection and significantly increased diarrhea severity after NoV infection. Simvastatin decreased proliferation of virus-specific and non-specific CD8 T cells in duodenum and virus-specific CD4 and CD8 T cells in spleen and significantly reduced numbers of intestinal mononuclear cells in vaccinated pigs. Furthermore, simvastatin significantly decreased numbers of duodenal CD4+IFN-\u03b3+, CD8+IFN-\u03b3+ and regulatory T cells and total duodenal activated CD4+ and CD8+ T cells in vaccinated pigs pre-challenge at PID 28. Following challenge, simvastatin prevented the IFN-\u03b3+ T cell response in spleen of vaccinated pigs. These results indicate that simvastatin abolished P particle vaccine-induced partial protection through, at least in part, impairing T cell immunity. The findings have specific implications for the development of preventive and therapeutic strategies against NoV gastroenteritis, especially for the elderly population who takes statin-type drugs.<\/jats:p>","DOI":"10.3390\/pathogens10070829","type":"journal-article","created":{"date-parts":[[2021,7,1]],"date-time":"2021-07-01T12:03:27Z","timestamp":1625141007000},"page":"829","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Simvastatin Reduces Protection and Intestinal T Cell Responses Induced by a Norovirus P Particle Vaccine in Gnotobiotic Pigs"],"prefix":"10.3390","volume":"10","author":[{"given":"Jacob","family":"Kocher","sequence":"first","affiliation":[{"name":"Center for Emerging, Zoonotic, and Arthropod-Borne Pathogens, Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tammy Bui","family":"Castellucci","sequence":"additional","affiliation":[{"name":"Center for Emerging, Zoonotic, and Arthropod-Borne Pathogens, Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ke","family":"Wen","sequence":"additional","affiliation":[{"name":"Center for Emerging, Zoonotic, and Arthropod-Borne Pathogens, Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guohua","family":"Li","sequence":"additional","affiliation":[{"name":"Center for Emerging, Zoonotic, and Arthropod-Borne Pathogens, Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xingdong","family":"Yang","sequence":"additional","affiliation":[{"name":"Center for Emerging, Zoonotic, and Arthropod-Borne Pathogens, Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shaohua","family":"Lei","sequence":"additional","affiliation":[{"name":"Center for Emerging, Zoonotic, and Arthropod-Borne Pathogens, Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xi","family":"Jiang","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Cincinnati Children\u2019s Hospital Medical Center, Cincinnati, OH 45229, USA"},{"name":"Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH 45229, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0709-5228","authenticated-orcid":false,"given":"Lijuan","family":"Yuan","sequence":"additional","affiliation":[{"name":"Center for Emerging, Zoonotic, and Arthropod-Borne Pathogens, Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,7,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1438","DOI":"10.3201\/eid2705.204756","article-title":"Global Trends in norovirus genotype distribution among children with acute gastroenteritis","volume":"27","author":"Cannon","year":"2021","journal-title":"Emerg. 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