Characterization of Simian immunodeficiency virus (SIV) envelope glycoprotein(gp120) antigenic determinants.

摘要

The identification of reliable immune correlates of AIDS vaccine protection in the SIV/monkey vaccine model has proven elusive, as standard assays of cellular and humoral immunity have failed to distinguish protective and nonprotective vaccine immunity. Using qualitative assays of antibody conformational dependence and avidity, we have previously described a complex evolution of envelope-specific antibody responses that is associated with the development of protective immunity in monkeys inoculated with attenuated strains of SIV. Further studies have demonstrated a significant correlation of these antibody maturation parameters with protective efficacy of other experimental vaccines in the SIV/monkey model.; The current studies were designed to examine in more detail the nature of the antibody maturation to attenuated SIV vaccines and to evaluate potential immune correlates of vaccine protection based on analysis of antibody responses to specific envelope domains, designated “domain-specific serology”. To achieve the analyses of predominantly conformationally-dependent antibody responses to the SIV envelope protein, we have produced a novel panel of recombinant HIV/SIV chimeric envelope antigens in which specific domains (both variable loop and conserved) of the SIV envelope gp120 have been substituted into the HIV-1 gp140 envelope background. These HIV/SIV chimeric envelope antigens have been used in serological assays to monitor the quantitative and qualitative progression of antibody responses associated with the immune maturation and development of protective immunity in monkeys inoculated with an attenuated SIV vaccine.; The serological assays show different levels of antibody responses to individual domains of the SIV envelope during immune maturation. These results show that there is a distinct maturation of antibody responses to individual, conformational domains of the SIV envelope glycoprotein. It was found that only chimeric proteins containing SIV variable loop domains demonstrated reactivity to polyclonal sera. Results suggested that antibody responses to the V3 and V4 loop domains of SIV gp120 could facilitate immune maturation and development of protective immunity. “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.