SAFETY AND EFFICACY OF HIGH-DOSE RHESUS-HUMAN REASSORTANT ROTAVIRUS VACCINES - REPORT OF THE NATIONAL MULTICENTER TRIAL

Objective. Rotavirus is a leading cause of morbidity and mortality fro m dehydrating gastroenteritis in infants and young children worldwide. Virtually every child is infected by age 4 years, justifying universa l childhood immunization when a safe and effective vaccine is availabl e. We report the results of a multicenter, placebo-controlled field tr ial in the United States of monovalent serotype 1 and tetravalent (TV) rhesus-human reassortant rotavirus vaccines (RRVs). Design. In this r andomized, double-blind trial, 1278 healthy infants ages 5 to 25 weeks received three oral doses of RRV serotype 1, RRV-TV, or a placebo at approximately 2, 4, and 6 months of age. Vaccines contained 4 x 10(5) plaque-forming units of virus. Gastroenteritis episodes were monitored , and severity was graded throughout one rotavirus season. Two stool s pecimens per episode were tested for rotavirus. Results. The incidence of reactions did not differ among treatment groups during the 5-day, postvaccination safety surveillance period for any of the three doses. Both vaccines significantly reduced the incidence of rotavirus gastro enteritis. Vaccination was most protective against serious rotavirus i llness; RRV-TV prevented 49% of rotavirus episodes, 80% of very severe episodes, and 100% of dehydrating rotavirus illness. Reduction of rot avirus disease by RRV-TV resulted in significantly fewer total episode s of gastroenteritis of all causes and an 82% reduction in all cases o f dehydrating diarrhea. Conclusion. RRV-TV is highly protective agains t very severe, dehydrating rotavirus gastroenteritis.