THE DEVELOPMENT OF MULTIVALENT BOVINE ROTAVIRUS (STRAIN WC3) REASSORTANT VACCINE FOR INFANTS

Laboratory and clinical studies have been directed toward development of a vaccine against rotavirus gastroenteritis in infants. First, bovi ne rotavirus strain WC3, which did not induce neutralizing antibodies to predominant human rotavirus (HRV) serotypes, was determined to be s afe and immunogenic; however, it was not protective in all efficacy tr ials. HRVs adapted to cell culture retained some virulence for infants , but when further attenuated by cold adaptation, they were poorly imm unogenic. Reassortant rotaviruses were designed to express HRV surface proteins VP7 (G) or VP4 (P) while retaining a bovine WC3 genome backg round, Reassortants containing either HRV surface protein and as few a s four bovine rotavirus genes were safe in infants, A monovalent WC3 r eassortant of serotype G1 specificity was 64%-100% protective in place bo-controlled trials. A quadrivalent WC3 reassortant vaccine with comp onents of HRV G1, G2, G3, and P[8] specificity induced 67% protection against all rotavirus disease in a multicenter efficacy trial.