Evaluation of rhesus rotavirus monovalent and tetravalent reassortant vaccines in US children. US Rotavirus Vaccine Efficacy Group

JAMA. 1995 Apr 19;273(15):1191-6.


Objective: To determine the safety and relative efficacy of two reassortant rhesus rotavirus vaccines over two rotavirus seasons.

Design: A prospective, double-masked, placebo-controlled trial.

Setting: Twenty-three centers in the United States.

Participants: A total of 1006 healthy infants between 4 and 26 weeks of age were enrolled, and 898 received three doses of vaccine or placebo.

Main outcome measures: Reactogenicity was determined by comparing the incidence of fever, diarrhea, and/or vomiting for 5 days after each dose of vaccine. Rotavirus IgA and neutralizing antibody to rhesus rotavirus and four rotavirus serotypes were measured in a subset of subjects. Relative efficacy was determined by comparing the incidence of rotavirus gastroenteritis after three doses of vaccine or placebo over two rotavirus seasons.

Results: Adverse reactions were mild and limited to a small but significant increase in the incidence of fever after the first dose of tetravalent but not monovalent vaccine. The relative efficacy against rotavirus disease over the 2 years of observation was 40% (98.3% confidence interval, 7% to 62%) for the monovalent and 57% (98.3% confidence interval, 29% to 74%) for the tetravalent vaccine. In post hoc analyses, the relative efficacy against very severe rotavirus gastroenteritis was 73% and 82% for monovalent and tetravalent vaccine recipients, respectively. Also, a 67% and 78% reduction in medical visits for rotavirus gastroenteritis was observed. Both vaccines protected against disease caused by serotype 1 rotavirus, but only the tetravalent vaccine reduced the incidence of disease caused by non-serotype 1 rotavirus infection detected in the second season. It is unclear, however, whether this result represents serotype-specific protection or a difference in the duration of protection.

Conclusions: Vaccination with both vaccines was safe and significantly reduced the incidence of rotavirus gastroenteritis, but only the tetravalent vaccine provided protection against disease caused by non-serotype 1 rotaviruses during the second year of follow-up.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Antibodies, Viral / biosynthesis
  • Antigens, Viral / analysis
  • Diarrhea, Infantile / microbiology
  • Diarrhea, Infantile / prevention & control*
  • Double-Blind Method
  • Humans
  • Immunization Schedule
  • Immunogenetics
  • Infant
  • Prospective Studies
  • Rotavirus / immunology*
  • Rotavirus Infections / immunology
  • Rotavirus Infections / prevention & control*
  • Rotavirus Vaccines*
  • Statistics as Topic
  • United States
  • Vaccination*
  • Vaccines, Attenuated / administration & dosage
  • Vaccines, Attenuated / immunology*
  • Viral Vaccines / administration & dosage
  • Viral Vaccines / immunology*


  • Antibodies, Viral
  • Antigens, Viral
  • Rotavirus Vaccines
  • Vaccines, Attenuated
  • Viral Vaccines
  • rhesus rotavirus vaccine