Grant: Doctoral Award - Frederick Banting and Charles Best Canada Graduate Scholarships

The HIV pandemic currently infects 40 million people worldwide, and over 60,000 people in Canada. Thousands of new infections occur annually in Canada, and millions around the world, suggesting that the most promising solution would be the creation of a vaccine. In Nairobi, Kenya, a cohort of commercial sex workers has been extensively studied since 1985. Within this group, there are long-term non-progressors (LTNPs) who progress to AIDS more slowly than normal, as well as rapid progressors, who progress more quickly. This cohort provides a unique opportunity to study and compare the natural responses of those people effectively controlling the virus and those who are not. Cytotoxic T cells (CTLs) are important in control of viral infections, but are very diverse and can have a wide array of responses. Deciphering which specific CTL responses are most effective against HIV will be crucial in creation of a vaccine. This study will characterize CTL responses of LTNPs vs rapid or normally progressing individuals, to elucidate why LTNPs have better viral control. The ability of their CTLs to control viral replication will be measured in vitro, providing valuable information on how the functional abilities of CTLs among these groups differ. Phenotypes will be measured using surface staining, to give a better idea of which specific CTLs are present. Also, the ability of CTLs to produce antiviral compounds or to rapidly divide will be measured, both of which have been implicated in viral control in the past. Lastly, the usage of T cell receptors (TCRs) will be analyzed by genetic sequencing, as individuals using more types of TCRs may be better able to fight off infections. Overall this study will provide a broad analysis of protective CTL responses. This knowledge of naturally effective responses to HIV will help to direct the production of an effective vaccine which could protect thousands of people in Canada, and around the world, from contracting this deadly disease.