Parenterally Administered P24-VP8* Nanoparticle Vaccine Conferred Strong Protection against Rotavirus Diarrhea and Virus Shedding in Gnotobiotic Pigs
by
Ashwin Ramesh 1
, Jiangdi Mao 1, Shaohua Lei 1, Erica Twitchell 1, Ashton Shiraz 1, Xi Jiang 2,3, Ming Tan 2,3 and Lijuan Yuan 1,*
Ashwin Ramesh 1, Jiangdi Mao 1, Shaohua Lei 1, Erica Twitchell 1, Ashton Shiraz 1, Xi Jiang 2,3, Ming Tan 2,3 and Lijuan Yuan 1,*
1
Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Tech, Blacksburg, VA 24060, USA
2
Division of Infectious Diseases, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH 45229, USA
3
Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH 45229, USA
*
Author to whom correspondence should be addressed.
Vaccines 2019, 7(4), 177; https://doi.org/10.3390/vaccines7040177
Received: 16 August 2019 / Revised: 23 October 2019 / Accepted: 24 October 2019 / Published: 6 November 2019
(This article belongs to the Special Issue Vaccines against RNA Viruses)
Current live rotavirus vaccines are costly with increased risk of intussusception due to vaccine replication in the gut of vaccinated children. New vaccines with improved safety and cost-effectiveness are needed. In this study, we assessed the immunogenicity and protective efficacy of a novel P24-VP8* nanoparticle vaccine using the gnotobiotic (Gn) pig model of human rotavirus infection and disease. Three doses of P24-VP8* (200 μg/dose) intramuscular vaccine with Al(OH)3 adjuvant (600 μg) conferred significant protection against infection and diarrhea after challenge with virulent Wa strain rotavirus. This was indicated by the significant reduction in the mean duration of diarrhea, virus shedding in feces, and significantly lower fecal cumulative consistency scores in post-challenge day (PCD) 1–7 among vaccinated pigs compared to the mock immunized controls. The P24-VP8* vaccine was highly immunogenic in Gn pigs. It induced strong VP8*-specific serum IgG and Wa-specific virus-neutralizing antibody responses from post-inoculation day 21 to PCD 7, but did not induce serum or intestinal IgA antibody responses or a strong effector T cell response, which are consistent with the immunization route, the adjuvant used, and the nature of the non-replicating vaccine. The findings are highly translatable and thus will facilitate clinical trials of the P24-VP8* nanoparticle vaccine.
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Keywords:
rotavirus nanoparticle vaccine; gnotobiotic pigs
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MDPI and ACS Style
Ramesh, A.; Mao, J.; Lei, S.; Twitchell, E.; Shiraz, A.; Jiang, X.; Tan, M.; Yuan, L. Parenterally Administered P24-VP8* Nanoparticle Vaccine Conferred Strong Protection against Rotavirus Diarrhea and Virus Shedding in Gnotobiotic Pigs. Vaccines 2019, 7, 177.
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