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. This project is part of a large consortium on AIDS vaccine development sponsored by the Gates Foundation and the International AIDS Vaccine Initiative (IAVI). A major goal of the consortium is to develop new approaches to AIDS vaccine using the rhesus macaque model to assess efficacy and in particular compare efficacy of all approaches in an identical challenge protocol. The specific goal of this project is to design, construct and test gene-deleted RhCMV vectors that have been optimized for immunogenicity and safety, and then comparatively assess both wildtype RhCMV vectors and gene-deleted RhCMV vectors in the standard efficacy protocol developed for the entire consortium. RhCMV vectors will be tested alone as well as in heterologous prime-boost protocols using DNA and adenovirus vectors as the heterologous prime or boost. This project has supported a second large efficacy trial of RhCMV/SIV vectors and has confirmed their ability to completely control mucosally-administered highly pathogenic SIV infection prior to systemic progressive infection. Moreover, under the auspices of this grant, we seek to develop attenuated CMV vectors that maintain immunogenicity, and efficacy, but have less capacity to cause disease. We have identified several candidates with promising characteristics that are being moved forward to formal safety and efficacy trials. Work to design CMV vectors with superior safety profiles has led to a number of basic discoveries in CMV pathobiology, in particular the biologic role of the US2-11 gene product-mediated MHC down-regulation by CMV, as indicated in the publication below.
Showing the most recent 10 out of 492 publications
