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.This study's goal is to develops a new vaccination strategy for the control of HIV/AIDS. The hypothesis is that vaccination strategies that enhance generation of central memory CD4 T cells enhance control of HIV infection. CD4 T cell help is very critical for the function of anti-viral killer CD8 T cells. Consistently, T cell vaccines that are currently in human trials (including our own DNA/MVA vaccine) elicit high levels of virus-specific CD4 T cells. However, these high levels of CD4 T cells represent a two-edge sword. On the one hand they provide help to anti-viral CD8 T cells and on the other hand they provide enhanced targets for the virus as HIV/SIV preferentially infects these virus-specific CD4 T cells. Our new approach is to develop CD4 T cells with central memory phenotype. These central memory cells express the chemokine receptor CCR7 but do not express viral co-receptor CCR5. As a result, these central memory CD4 T cells do not become targets for the virus, do not enhance viral infection but retain their ability to help anti-viral CD8 T cells. Faster clearance of antigen has been shown to generate central memory T cells.
Our aim i s to generate central memory CD4 T cells by co-expressing a mutated caspase-3 that will result in faster clearance of antigen.
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