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

J Infect Dis. 2009 Aug 1;200(3):421-9. doi: 10.1086/600104.

Abstract

Background: Rotavirus infections cause approximately 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 X 10(4) focus-forming units (ffu) and 182 received a dose of 1 X 10(5) 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 X 10(4) ffu and 1 X 10(5) ffu, respectively; the differences between these groups and placebo recipients were statistically significant.

Conclusions: Three administrations of vaccine doses of 1 X 10(4) ffu and 1 X 10(5) ffu were safe. The 1 X 10(5)-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. Clinical trials registration. NCT00439660 and ISRCTN57452882 .

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Viral / blood
  • Dose-Response Relationship, Immunologic
  • Double-Blind Method
  • Female
  • Humans
  • Infant
  • Male
  • Rotavirus / immunology
  • Rotavirus Infections / immunology
  • Rotavirus Vaccines / adverse effects*
  • Rotavirus Vaccines / immunology*
  • Vaccines, Attenuated / adverse effects
  • Vaccines, Attenuated / immunology
  • Virus Shedding

Substances

  • Antibodies, Viral
  • Rotavirus Vaccines
  • Vaccines, Attenuated

Associated data

  • ClinicalTrials.gov/NCT00439660
  • ISRCTN/ISRCTN57452882