Abstract
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.
Highlights
Rotavirus is the leading cause of severe infantile diarrhea worldwide
Vaccinated and control Gn pigs were challenged with virulent Wa strain (G1P[8]) HRV (VirHRV) at PID 28 and were monitored daily for clinical signs of infection and virus shedding from postchallenge day (PCD) 1 to PCD 7
The preserved film vaccine significantly reduced the area under the curve (AUC) of diarrhea compared to the liquid vaccine and placebo groups (6.8, 9.7, and 10.6, respectively) (Table 1)
Summary
Rotavirus is the leading cause of severe infantile diarrhea worldwide. Even with live oral vaccines widely available since 2006, rotavirus infections are still responsible for the majority of cases of diarrheal disease in children globally, accounting for up to 50% of these cases [1,2]. RotaTeq® (Merck, Kenilworth, NJ, USA) and Rotarix® (GSK, Brentford, UK) are both prequalified for worldwide use by the World Health Organization (WHO), and as of 2009, WHO has recommended that HRV vaccines be incorporated into all national immunization programs [6]. These vaccines are highly efficacious (~90%) at preventing severe rotaviral diarrhea in properly vaccinated children in the United States and other high-income countries, but their efficacies are much lower in low- to middle-income countries (LMIC) (39–70%) and the cause is multifaceted [1,7,8,9,10,11,12,13]
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