NEUTRALIZING ANTIBODY COVERAGE FOR CTL VACCINES (PROJECT 2)

Emory University, Atlanta GA

Investigators

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Abstract

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Hildegund Ertl is the program director of a recently awarded program project grant, "Correlates of Protection against a SIV/SHIV Challenge" and Ruth Ruprecht is the PI of Project 2. This subcontract to project 2 provides access to nonhuman primates and facilitates research involving immunoprophylaxis against SHIV as a model for prophylactic prevention of HIV transmission, as designed by Drs. Ruprecht of Ertl. All immunizations, inoculations, bleedings, and other samplings are performed by animal research staff at the Yerkes Main Station. Additionally, as directed by Drs. Ertl and Ruprecht, virus dilutions and virus titration assays are performed by staff of the Novembre laboratory. Project 2 seeks to test the hypothesis that a potent CTL vaccine can be protective if additional coverage is provided by neutralizing antibodies (nAbs). We are using passive immunization with polyclonal IgG isolated from rhesus macaques with high-titer, broadly reactive anti-HIV nAbs in responses to infection with simian-human immunodeficiency virus (SHIV) strains encoding R5 env genes of recently transmitted HIV clade C (HIV-C). We seek to combine passive SHIVIG immunization with active vaccination based upon the optimal CTL vaccine as determined by mucosal immunogenicity studies. Our data will provide a blueprint towards developing combined-modality vaccines that induce both CTL and nAb responses. We will correlate in vitro neutralization in PBMC assays to in vivo protection, thus facilitating optimization of nAb response-based vaccines. As such, our combined-modality approach and its correlation to in vitro neutralization parameters address an important topic in AIDS vaccine development.