This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.We are using a rhesus macaque model of HIV infection and AIDS to develop potential vaccine strategies against the clade C strain of HIV, the world's most prevalent strain. For testing the efficacy of potential vaccines against HIV clade C, we developed hybrid viruses, called SHIVs, by combining genetic components of a monkey AIDS virus with a portion of HIV called envelope; we have developed two such viruses using envelopes from HIV clade C strains isolated from two infected African infants. Our approach to vaccine development has been to generate: 1) immune cell-based responses to multiple viral components, and 2) neutralizing antibody-based immunity to envelope. The envelope of each HIV strain is unique, and to more closely mimic reality where vaccinated individuals will not be exposed to HIV strains identical to that used to prepare the vaccine components, we deliberately challenged our vaccinated monkeys with SHIVs in which the envelopes are mismatched compared to the envelope used for vaccination. In our study, monkeys that were immunized as infants against three different structural components of SHIV showed protection against both low-dose and high-dose challenges with two forms of a clade C SHIV, including one case of complete protection.We are also following a set of animals, previously vaccinated and/or exposed to clade C SHIVs that have maintained high levels of envelope-specific antibodies that can neutralize many diverse strains of HIV. We are analyzing the fine-specificity of the antibody responses in these animals in order to identify specific sites of envelope recognized by neutralizing antibodies that are common among different HIV strains. This information will be important for the design of vaccine components to raise antibodies that would neutralize a broad range of HIV strains in vaccinated humans.
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