Epitope specificity of vaccine-induced anti-HIV IgG /IgA

Duke University, Durham NC

Investigators

Abstract

DESCRIPTION: (Provided by Applicant) Published studies with HIV-infected subjects suggest that anti-HIV IgA serum and mucosal antibodies may be specific for the conserved neutralizing gp41 epitope ELDKWA while anti-HIV IgG antibodies from the same subjects are not. Other studies suggest that anti-HIV IgA antibodies from HIV-exposed but uninfected persons recognize gp41 epitopes that are different than gp41 epitopes recognized by anti-HIV IgA antibodies from HIV-infected individuals. Recent studies in mice indicated that mucosal IgA responses may be produced by a population of B cells that is activated peripherally in the absence of T cell help and in uMT mice that lack IgG and IgM responses and normal systemic B cell development. Collectively, these results suggest that the induction and regulation of antigen-specific IgA responses is very different than the induction and regulation of antigen-specific IgG and IgM responses and that many factors may contribute to the specificity of antibody responses induced, especially in the out-bred human population. Therefore, carefully controlled studies are required to determine if the route of immunization, adjuvant, antigen dose, use of live replicating vaccine vectors and/or the responding population of B cells affects the specificity of anti-HIV IgG and IgA antibody responses induced after vaccination with HIV antigens. Studies proposed in this application will answer these questions. Our long-term goal is to identify immunization strategies that will induce systemic and mucosal antibody responses specific for conserved neutralizing epitopes in HIV-1. Our specific aims are: Specific Aim 1: Determine if the route of immunization, antigen dose, adjuvant and/or use of live viral vaccine vectors affects the epitopes recognized by anti-HIV serum and mucosal IgG and IgA induced after systemic or mucosal immunization with HIV-1 gp41 or vaccinia gp41. Specific Aim 2: Determine if mucosal inoculation of uMT mice (mice deficient in systemic IgG and IgM B cell responses) with recombinant vaccinia gp41MN induces IgA responses that recognize gp41 epitopes that are different than gp41 epitopes recognized by IgA from wild-type mice inoculated with recombinant vaccinia gp41MN.