Abstract
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.
Highlights
Human rotavirus (HRV) is a leading cause of severe, dehydrating gastroenteritis in children under five years of age
Vaccinated and control Gn pigs were challenged with VirHRV at post-inoculation day (PID) 28 and were monitored daily for clinical signs and virus shedding from post-challenge day (PCD) 1 to PCD 7
Gn pigs that were administered with P24-VP8* vaccine had a significantly delayed onset of diarrhea, a significantly reduced duration of diarrhea, significantly lower mean diarrhea scores on PID
Summary
Human rotavirus (HRV) is a leading cause of severe, dehydrating gastroenteritis in children under five years of age. A combination of factors have been suggested to be responsible for the lower efficacy, which have been reviewed and discussed in detail by Arnold [8] and Desselberger [9] Both these live vaccines have been linked to a low risk of intussusception (1–7 cases per 100,000 vaccinated infants) as a result of the vaccine rotavirus (RV) strains replicating in the intestines [10,11], and have remained expensive even after Gavi, the Vaccine Alliance, subsidization [12], in resource-deprived countries. These scenarios have increased the demand for a safer, more cost-effective, and more efficacious vaccine, especially in LMICs that can be administered.
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