Core B will actively participate in all vaccination studies by processing secretions collected from vaccinerecipients and quantitating SIV- or HIV-specific mucosal IgA and IgG antibodies by ELISA in thesespecimens. Core B will also provide expert advice regarding optimal timing and methods for collection ofsecretions. Blinded frozen specimens will be shipped to Core B for both experimental antibody analyses andfor quality control assurance tests. Justification for measurement of mucosal antibodies in vaccinatedmacaques and humans is based on results of preliminary studies which suggest that 1) parenteralimmunization with DNA/MVA vaccine can induce strong and long-lived antiviral rectal antibody responses ifGM-CSF is included as adjuvant, and that 2) induction of antiviral mucosal IgA antibody responses isassociated with protection against immunodeficiency virus infection.
In Aim I, we will measure binding antibodies to SIVmac251 rgp130 and non-envelope-containingSIVmac251 viral lysate to show that immunization of female rhesus macaques with GM-CSF-adjuvantedSIVmac239 DNA/MVA or MVA/MVA vaccine induces SIV envelope- and gag/pol-specific IgA and IgG inrectal and vaginal secretions. SIV-specific antibodies will be quantitated immediately before and at intervalsafter rectal SIVmac251 challenge to determine if reductions in viremia correlate better with levels of anti-envversus anti-gag/pol antibodies present in secretions before or after challenge.
In Aim II preclinal safety andimmunogenicity studies with macaques, we will evaluate a GM-CSF-adjuvanted Clade C DNA/MVA orMVA/MVA vaccine for its ability to induce rectal and genital tract antibodies to Clade C HIVczm rgp120 andTanzanian HIV viral lysate. In Phase I and II studies of Aim III, GM-CSF-adjuvanted Clade C DNA/MVA orMVA/MVA vaccine will similarly be evaluated for ability to induce Clade C HIV-specific IgA and IgGantibodies 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 shouldprove invaluable for evaluating antibody responses to other Clade C HIV vaccine candidates. The results ofthe SIV vaccine/challenge studies should also indicate whether induction of anti-env or anti-gag/pol mucosalantibody responses could be used as an immune correlate for predicting HIV vaccine efficacy in humans.