Homotypic and Heterotypic Epitope-Specific Antibody Responses in Adult and Infant Rotavirus Vaccinees: Implications for Vaccine Development

Abstract

Sera from infants and adults who received a live, attenuated monovalent rotavirus vaccine of serotype 1, 2, 3, or 4 VP7 specificity and rhesus rotavirus (RRV) VP4 specificity were analyzed for serotype-specific antibody responses by an epitope blocking immunoassay (EBA) and by neutralization. Although the assays correlated well, responses to the individual neutralization proteins or to different defined antigenic sites on the same protein could be distinguished only by EBA. In general, adult vaccinees exhibited both a homotypic response to the immunizing strain and a heterotypic response to other serotypes. Infant vaccinees less than 6 months old also had a homotypic antibody response but developed significantly fewer heterotypic responses than adults (1.2% and 59%, respectively; P less than .0001). In addition, postvaccination sera from vaccinees who developed naturally occurring rotavirus diarrhea during an efficacy trial of RRV (MMU-18006) or RIT 4237 vaccine were analyzed for serotype-specific responses. The data suggest that the inability to mount a heterotypic antibody response to the infecting serotypes in young infants may have been an important factor in failure of the vaccines to induce protection.