VACCINE REGIMENS TO INDUCE CD4+ AND CD8+ T CELLS AGAINST SIV EPITOPES

University Of Wisconsin-Madison, Madison WI

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Abstract

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. Objective: To compare four novel vaccine regimens to induce CD4+ and CD8+ T Cells against SIV epitopes. Recent failures in clinical HIV vaccines have underscored the importance of more thoroughly evaluating basic science of HIV as well as testing new vaccine regimens and vectors. In an effort to overcome the limitations of more traditional vector-based vaccines, our laboratory has developed several novel immunization strategies. These new methods will allow us to directly prime specific T cell responses in a manner that previously has been impossible with other vaccine vectors and regimens. This should allow us to dissect the contributions of specific T cell responses in the control of SIV replication- the roles of both subdominant CD8+ T cells and virus-specific CD4+ T cells. In the R21 phase of this grant, we will compare four novel vaccination regimens: peptide-pulsed dendritic cells, peptide-conjugated nanobeads, peptide-pulsed PBMC, and SIV peptides fused to a Hepatitis B core antigen (HBcAg) carrier gene. Subproject progress: The MHC Typing Core of the Primate Center successfully typed six MHC class II, Mamu-DR[unreadable]w*606, positive animals in the Wisconsin National Primate Breeding Colony- to be used in groups one and two of the R21 phase. In addition, we selected six MHC class I Mamu-A*01 positive animals for the third and fourth groups of the R21 phase. Each of the selected Mamu-A*01-restricted CD8 epitopes were inserted into individual HBcAg backbones. Recombiworks has designed the HBcAg constructs, completed and sequenced the plasmids to confirm correct construction. Dr. Deborah Fuller has analyzed the HBcAg vectors for expression of the HepB core particles. After initial in vitro testing, two autologous peptide-pulsed dendritic cell vaccinations have been completed. The final dendritic cell prime is scheduled for Wednesday, February 11th, 2009. The HBcAg vaccinations are in the final stages of construct analysis and confirmation with the first HBcAg prime scheduled for Wednesday, March 4th, 2009 with each subsequent vaccination four weeks apart. No detectable CD4+ T cell responses have been seen after the first or second dendritic cell vaccination;however, this is to be expected as no responses were seen in a preliminary pilot study. During this upcoming year, we plan to complete these immunogenicity vaccinations and hopefully move on to the R33 phase of the grant.