PRE-CLINICAL IMMUNOGENICITY STUDIES OF CHIMPANZEE ADENOVIRUS VECTORS

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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. The generation of an effective AIDS vaccine is greatly complicated by our incomplete knowledge of the correlates of immune protection during HIV infection. This project focuses on the immunogenicity and protection from SIV challenge conferred by chimpanzee adenovirus (AdC)-based candidate AIDS vaccines. Over the past year we concluded the analysis and published the results of an immunization and challenge study using an AdC6SIVgag vector boosted with AdC7-gDSIVgag (a vector expressing Gag as a fusion protein within the immunostimulatoryHSV-1gD molecule). In addition, we made significant progress on an additional large study of the safety, immunogenicity and protection from pathogenic SIV challenge of two combinations of the SIVgag/tat expressing AdC vectors, AdC6 and AdC7, that we used in a sequential heterologous prime-boost regimen in 30 RMs (i.e., AdC6-SIVgag/tat followed by AdC7-SIVgag/tat and AdC7-SIVgag/tat followed by AdC6-SIVgag/tat). We have completed the immunization phase, and we are now in the challenge phase of the experiment, which involves up to 15 low-dose intra-rectal challenges with SIVmac251 that were administered every two weeks with weekly monitoring of SIV viremia. Currently 28 out of 30 RMs have been infected, and thus we expect to complete the challenge phase within the next month. At that point the animals will be followed for an additional 6 months after infection to monitor their level of disease progression (i.e., set point viral load, CD4 depletion, survival). Ultimately we hope that this study will allow us to assess the efficacy in the SIV NHP model of gag/tat expressing AdC-based candidate AIDS vaccines