WC3 REASSORTANT VACCINES IN CHILDREN

Bovine rotavirus strain WC3 (P7[5], G6) administered at the 12th passa ge level was well tolerated clinically in infants and efficiently indu ced serum virus neutralizing antibody (VNA) with bovine rotavirus G6 s pecificity. The protective efficacy of WC3 vaccine against all rotavir us disease was inconsistent, varying in four separate trials from 76% to 0%; some selective protection against severe disease was seen in al l trials. WC3 reassortants containing the gene for an individual human rotavirus VP7 (G) or VP4 (P) surface antigen were also well tolerated , but preferentially induced VNA to the WC3 parent. Efficacy trials of human G1 VP7 reassortant WI79-9 (P7[5], G1) consistently led to >60% protection against all rotavirus disease. A quadrivalent WC3 reassorta nt vaccine was developed to contain four separate monovalent reassorta nts expressing human rotaviruses surface proteins G1, G2, G3, and P1A [8] respectively. In a multicenter trial including 439 infants, this v accine induced 67.1% protection against all rotavirus disease (defined as positive for rotavirus antigen by ELISA only [p=<0.001]) and 72.6% protection when the standard for rotavirus diagnosis was a positive t est of stool for both rotavirus antigen by ELISA and rotavirus RNA by electropherotype analysis (p=<0.001). In this trial, episodes of the m ost severe rotavirus disease (clinical severity score >16.0, eight cas es) occurred only in placebo recipients.