Research Project
7280625
Core B will actively participate in all vaccination studies by processing secretions collected from vaccine recipients and quantitating SIV- or HIV-specific mucosal IgA and IgG antibodies by ELISA in these specimens. Core B will also provide expert advice regarding optimal timing and methods for collection of secretions. Blinded frozen specimens will be shipped to Core B for both experimental antibody analyses and for quality control assurance tests. Justification for measurement of mucosal antibodies in vaccinated macaques and humans is based on results of preliminary studies which suggest that 1) parenteral immunization with DNA/MVA vaccine can induce strong and long-lived antiviral rectal antibody responses if GM-CSF is included as adjuvant, and that 2) induction of antiviral mucosal IgA antibody responses is associated with protection against immunodeficiency virus infection. In Aim I, we will measure binding antibodies to SIVmac251 rgp130 and non-envelope-containing SIVmac251 viral lysate to show that immunization of female rhesus macaques with GM-CSF-adjuvanted SIVmac239 DNA/MVA or MVA/MVA vaccine induces SIV envelope- and gag/pol-specific IgA and IgG in rectal and vaginal secretions. SIV-specific antibodies will be quantitated immediately before and at intervals after rectal SIVmac251 challenge to determine if reductions in viremia correlate better with levels of anti-env versus anti-gag/pol antibodies present in secretions before or after challenge. In Aim II preclinal safety and immunogenicity studies with macaques, we will evaluate a GM-CSF-adjuvanted Clade C DNA/MVA or MVA/MVA vaccine for its ability to induce rectal and genital tract antibodies to Clade C HIVczm rgp120 and Tanzanian HIV viral lysate. In Phase I and II studies of Aim III, GM-CSF-adjuvanted Clade C DNA/MVA or MVA/MVA vaccine will similarly be evaluated for ability to induce Clade C HIV-specific IgA and IgG antibodies in genital tract and rectal secretions of male and female human volunteers. The reference standards and procedures that will be developed and validated in these studies should prove invaluable for evaluating antibody responses to other Clade C HIV vaccine candidates. The results of the SIV vaccine/challenge studies should also indicate whether induction of anti-env or anti-gag/pol mucosal antibody responses could be used as an immune correlate for predicting HIV vaccine efficacy in humans.
