Background: The identification of reliable immune correlates of AIDS vaccine protection in the SIV/monkey vaccine model has proven elusive. Using qualitative assays of antibody conformational dependence and avidity, we have previously described a complex evolution of envelope-specific antibody responses associated with the development of protective immunity in monkeys inoculated with attenuated strains of SIV. The current studies were designed to examine the nature of the antibody maturation to attenuated SIV/17E and evaluate potential immune correlates of vaccine protection based on the analysis of antibody responses to specific envelope domains, designated “domain-specific” serology.

Methods: To achieve the analyses of predominantly conformationally-dependent antibody responses, we have produced a novel panel of HIV/SIV chimeric envelope antigens in which specific domains of the SIV envelope have been substituted into the HIV-1 envelope background and expressed in the vaccinia system. These chimeric envelope antigens have been used in serological assays to monitor the quantitative and qualitative progression of antibody responses associated with the immune maturation in monkeys inoculated with an attenuated SIV vaccine.

Results: The results of these serological assays show different levels of antibody responses to individual domains of the SIV envelope during immune maturation. Qualitative antibody to these individual envelope domains also varies. These results show that there is a distinct maturation of antibody responses to individual, conformational domains of the SIV envelope glycoprotein that can be predictive of immune maturation protection in these monkeys.

Conclusions: The results of these domain-specific serological assays reveal new aspects of the antibody maturation to attenuated SIV vaccines that better characterize the nature of antibody responses associated with mature, protective immunity and that provide novel parameters that can be evaluated further as potential immune correlates of vaccine protection.