Difficulties related to storage and transport of currently available live oral
rotavirus vaccines can have detrimental consequences on the efficacy of the
vaccines. Thus, there is a great need for thermostable
vaccines that can eliminate the necessity for cold chain storage or reconstitution before administration. In this study, we developed a dissolvable oral polymeric film comprised of a live attenuated thermostable tetravalent rhesus-human reassortant
rotavirus vaccine (
RRV-TV)
powder and
antacid (CaCO3). Immunogenicity and protective efficacy of the
vaccine after buccal delivery was evaluated in the gnotobiotic pig model of human rotavirus (HRV)
infection and
diarrhea. Two doses of the
vaccine were highly immunogenic and conferred strong protection against virus shedding and
diarrhea upon challenge with a high dose of a virulent G1 HRV in gnotobiotic pigs. Those pigs vaccinated with the preserved film
vaccine had significantly delayed onset of
diarrhea; reduced duration and area under the curve of
diarrhea; delayed onset of fecal virus shedding; and reduced duration and peak of fecal virus shedding titers compared to pigs in both the placebo and the reconstituted liquid oral
RRV-TV vaccine groups. Associated with the strong protection, high titers of serum virus neutralization
antibodies against each of the four
RRV-TV mono-reassortants and G1 HRV-specific serum
IgA and
IgG antibodies, as well as intestinal
IgA antibodies, were induced by the preserved film
vaccine. These results demonstrated the effectiveness of our thermostable buccal film
rotavirus vaccine and warrant further investigation into the promise of the novel technology in addressing drawbacks of the current live oral HRV
vaccines.