EVOLUTION OF ENVELOPE-SPECIFIC ANTIBODY-RESPONSES IN MONKEYS EXPERIMENTALLY INFECTED OR IMMUNIZED WITH SIMIAN IMMUNODEFICIENCY VIRUS AND ITS ASSOCIATION WITH THE DEVELOPMENT OF PROTECTIVE IMMUNITY

Previous studies of attenuated simian immunodeficiency virus (SIV) vac cines in rhesus macaques have demonstrated the development of broad pr otection against experimental challenge, indicating the potential for the production of highly effective immune responses to SIV antigens. H owever, the development of this protective immune status was found to be critically dependent on the length of time postvaccination with the attenuated virus strain, suggesting a necessary maturation of immune responses, In this study, the evolution of SIV envelope-specific antib odies in monkeys experimentally infected with various attenuated strai ns of SIV was characterized by using a comprehensive panel of serologi cal assays to assess the progression of antibodies in longitudinal ser um samples that indicate the development of protective immunity, In pa rallel studies, we also used the same panel of antibody assays to char acterize the properties of SN envelope-specific antibodies elicited by inactivated whole-virus and envelope subunit vaccines previously repo rted to be ineffective in producing protective immunity, The results o f these studies demonstrate that the evolution of protective immunity in monkeys inoculated with attenuated strains of SIV is associated wit h a complex and lengthy maturation of antibody responses over the firs t 6 to 8 months postinoculation, as reflected in progressive changes i n antibody conformational dependence and avidity properties, The estab lishment of long-term protective immunity at this time in general para llels the absence of further detectable changes in antibody responses and a maintenance of relatively constant antibody titer, avidity, conf ormational dependence, and the presence of neutralizing antibody for a t least 2 years postinoculation, In contrast to the mature antibody re sponses elicited by the attenuated SN vaccines, the whole-virus and en velope subunit vaccines in general elicited only immature antibody res ponses characterized by poor reactivity with native envelope proteins, low avidity, low conformational dependence, and the absence of neutra lization activity against the challenge strain, Thus, these studies es tablish for the first time an association between the effectiveness of experimental vaccines and the capacity of the vaccine to produce a ma ture antibody response to SIV envelope proteins and further indicate t hat a combination of several antibody parameters (including titer, avi dity, conformational dependence, and virus neutralization) are superio r to any single antibody parameter as prognostic indicators to evaluat e candidate AIDS vaccines.