A dose-escalation safety and immunogenicity study of live attenuated oral rotavirus vaccine 116E in infants: a randomized, double-blind, placebo-controlled trial

Abstract

Background: Rotavirus infections cause ~122,000 deaths among Indian children annually. Methods: The neonatal rotavirus candidate vaccine 116E was tested in a double-blind, placebo-controlled dose-escalation trial in India. Two doses of the Vero cell-adapted vaccine were evaluated. One hundred eighty-seven infants received a vaccine dose of 1×10⁴ focus-forming units (ffu) and 182 received a dose of 1×10⁵ ffu in a 1:1 randomization with placebo recipients. Infants received the vaccine at 8, 12, and 16 weeks, separately from routine vaccines. Results: No significant differences in clinical adverse events or laboratory toxicity were observed between vaccine and placebo recipients. There were no vaccine-related serious adverse events. A 4-fold increase in rotavirus immunoglobulin A titer was observed in 66.7% and 64.5% of infants after the first administration and in 62.1% and 89.7% of infants after 3 administrations of doses of 1×10⁴ ffu and 1×10⁵ ffu, respectively; the differences between these groups and placebo recipients were statistically significant. Conclusions: Three administrations of vaccine doses of 1×10⁴ ffu and 1×10⁵ ffu were safe. The 1×10⁵-ffu dose of 116E demonstrated a robust immune response after 3 administrations. These favorable results warrant further development of the vaccine candidate and provide optimism that vaccinating infants in the developing world will prevent serious sequelae of rotavirus infection.