EVALUATION OF RHESUS ROTAVIRUS MONOVALENT AND TETRAVALENT REASSORTANTVACCINES IN US CHILDREN

Objective.-To determine the safety and relative efficacy of two reasso rtant 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 heal thy infants between 4 and 26 weeks of age were enrolled, and 898 recei ved three doses of vaccine or placebo. Main Outcome Measures.-Reactoge nicity was determined by comparing the incidence of fever, diarrhea, a nd/or vomiting for 5 days after each dose of vaccine. Rotavirus IgA an d neutralizing antibody to rhesus rotavirus and four rotavirus serotyp es were measured in a subset of subjects. Relative efficacy was determ ined by comparing the incidence of rotavirus gastroenteritis after thr ee doses of vaccine or placebo over two rotavirus seasons. Results.-Ad verse reactions were mild and limited to a small but significant incre ase in the incidence of fever after the first dose of tetravalent but not monovalent vaccine. The relative efficacy against rotavirus diseas e 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 relativ e efficacy against very severe rotavirus gastroenteritis was 73% and 8 2% for monovalent and tetravalent vaccine recipients, respectively. Al so, a 67% and 78% reduction in medical visits for rotavirus gastroente ritis was observed. Both vaccines protected against disease caused by serotype 1 rotavirus, but only the tetravalent vaccine reduced the inc idence of disease caused by non-serotype 1 rotavirus infection detecte d in the second season. It is unclear, however, whether this result re presents serotype-specific protection or a difference in the duration of protection. Conclusions.-Vaccination with both vaccines was safe an d significantly reduced the incidence of rotavirus gastroenteritis, bu t only the tetravalent vaccine provided protection against disease cau sed by non-serotype 1 rotaviruses during the second year of follow-up.