Evaluation of RIX4414, A live, attenuated rotavirus vaccine, in a randomized, double-blind, placebo-controlled phase 2 trial involving 2464 Singaporean infants

Background. At present, no rotavirus vaccine is commercially available for use worldwide. Hence, a live, attenuated monovalent vaccine was developed with human strain RIX4414 (G1P1A P[8] specificity). Vaccination trials involving infants are ongoing in developed and developing countries. Methods. This study was a randomized, double-blind, placebo-controlled trial conducted at pediatric hospitals and polyclinics in Singapore for the evaluation of the immunogenicity, reactogenicity, and efficacy of 2 oral doses of RIX4414. In total, 2464 healthy infants (who were 11-17 weeks old when the first dose was administered, which is in accordance with the local immunization schedule) were enrolled to receive RIX4414 at 3 concentrations of virus (10(4.7), 10(5.2), or 10(6.1) focus-forming units) or placebo at 1-month intervals, concomitantly with routinely administered infant vaccines. Results. The RIX4414 vaccine was highly immunogenic, and virtually all vaccine recipients (98% - 100%) experienced "vaccine take" (i.e., a combined immunogenicity end point based on seroconversion and/or shedding of RIX4414 in postvaccination stool samples) after receipt of 2 doses at all 3 dosage levels. Depending on the virus concentration, the anti - rotavirus IgA seroconversion rate varied from 76% (95% confidence interval [CI], 68%-83%) to 91% (95% CI, 85%-95%). Two doses of RIX4414 were well tolerated, with no increase in high fever, severe diarrhea, or vomiting after either dose or with increased viral concentration, compared with placebo. There was no observed interference with routine vaccinations of infants when RIX4414 was coadministered. The calculated efficacy of RIX4414 against rotavirus gastroenteritis was 82% (P = .046); however, this result was considered to be of limited conclusive value because of the low number of rotavirus gastroenteritis episodes identified during the follow-up period. Conclusions. The live, attenuated rotavirus vaccine (RIX4414) was well tolerated and highly immunogenic in Singaporean infants. The immunogenicity of routinely administered infant vaccines was not impaired by concomitant administration of RIX4414 vaccine.