Evidence suggests that the length of clinical latency of HIV infection may be determined by the levels of persisting viral load and control of viremia is primarily effected by cytolytic T lymphocytes (CTL). Although individuals often mount vigorous CTL responses to HIV during the course of natural infection, the naturally induced CTL responses are usually not sufficient because infection eventually worsens and develops into AIDS. Therefore, boosting the initial CTL responses through vaccination is thought to be beneficial by reducing viral load low enough so that infected individuals become long-term asymptomatic. The goal of this project is to facilitate the development of a HIV vaccine that will elicit a strong and long-lasting CTL response by better understanding the nature of T cell memory and providing an easy and reliable assay for memory T cells. To this end we will construct a transgenic mouse strain in which responding T cells and surviving memory T cells are marked by the expression of an exogenous gene. Using the novel mouse model, we will systematically evaluate CTL responses and memory CTLs to protein and DNA vaccines of hsp70-SIV fusions and different vaccination protocols to identify the most effective vaccine candidate and vaccination strategy for further evaluation in primates and humans.
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