This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. In association with the Dana Farber Cancer Institute, we are using the rhesus macaque model of HIV infection and AIDS to develop potential vaccine strategies against the Clade C strain of HIV (HIV-C) the world's most prevalent strain. The grant supplement specifically seeks to determine the correlates of protection in a vaccinated Rhesus with long-lived antiviral immunity. For efficacy testing of potential vaccines, we have developed a series of hybrid viruses, (SHIVs) by combining genetic components of simian immunodeficiency virus with envelope genes cloned directly from Zambian pediatric samples. SHIVs are then adapted to rhesus macaques generating challenge stocks capable of inducing infection via mucosal routes and sustaining viral loads and disease to test vaccine efficacy. Of interest is the fact that the Env of SHIV1157ipd3 was isolated from a newborn who has maintained high CD4 levels in spite of high viral loads for 10 years while Env from SHIV2873Nip was isolated from a newborn that developed AIDS and died at 9 months, suggesting Env as a pathogenic determinant across species. Vaccine efficacy is purposely tested against challenges with SHIV-C isolates that are heterogonous to the isolates from which the vaccine antigens are developed to mimic reality field conditions. We are also analyzing the fine-specificity of the antibody responses in these animals to identify specific sites of envelope able to induce broadly cross-neutralizing antibodies across HIV strains, a key component of new HIV vaccines.
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