A MODEL FOR THE MATURATION OF PROTECTIVE ANTIBODY-RESPONSES TO SIV ENVELOPE PROTEINS IN EXPERIMENTALLY IMMUNIZED MONKEYS

Studies using live attenuated virus vaccines in the simian immunodefic iency virus (SIV) rhesus macaque model have demonstrated broad protect ion against experimental challenge. Protection in these studies was fo und to be critically dependent on the length of time postvaccination, suggesting that protective immunity involves a necessary maturation of immune responses. The current study characterizes the evolution of pr otective envelope-specific antibody responses from monkeys inoculated with the highly attenuated SIV/17E-Cl virus vaccine. For comparison, t he same antibody assays were used to characterize the properties of SI V envelope-specific antibodies elicited by inactivated whole virus and envelope subunit vaccines that failed to provide protection from expe rimental virus challenge. Results of these studies identify a continuo us and complex maturation of envelope-specific antibody responses duri ng the first six to eight months postinfection. Furthermore, the time required for maturation of SIV envelope-specific antibodies parallels the time required for the development of protective immunity against e xperimental challenge with heterologous strains of SIV. While no singl e immune correlate of protection has been identified, we suggest that a combination of antibody parameters may serve as prognostic indicator s in the: development of candidate AIDS vaccines.