ENHANCED IMMUNOGENICITY OF CHIMERIC SHIV VLPS

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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. Development and implementation of an effective HIV vaccine that would prevent infection is a logical approach to controlling the spread of the disease. Infection of rhesus macaques with the simian immunodeficiency virus (SIV) is the best animal model for HIV infection in humans. The goal of this project is to determine the immunogenicity of virus-like particles (VLPs) and enhanced immunogenicity of chimeric influenza hemagglutinin (HA) SHIV VLPs and CD40L/SHIV VLPs on the non-human primate model, we propose to study and compare the immunogenicity of SHIV VLPs, HASHIV VLPs and CD40L/SHIV VLPs in the rhesus macaques model to confirm the immunogenicity data obtained from the mouse model. We will immunize SHIV VLPs, HASHIV VLPs, and CD40L/SHIV VLPs intranasally at 0,1 , 2, 3,10,and 27 weeks. Blood, mucosal secretions (saliva, broncho-alveolar lavages and feces) will be collected at several time points pre- and post-vaccination (0, 5, IO, 12, 24, 27, 29, 32, 40 wks). Inguinal and axillary lymph nodes will be collected at 0, 12 and 40 weeks. ELISA antibody to SIV Gag and HIV Env, neutralizing antibody across different HIV strains, and CTL responses to SIV Gag and HIV Env will be tested and compared with different VLPs immunization. We expect that enhanced immune responses will be observed in chimeric HNSHIV VLP and CD40L/SHIV VLP immunized mice. Ultimately, information obtained from the monkey model will form a basis for the future development of a successful HIV vaccine in human trials.