What Constitutes a Protective CTL Response in HIV-1 Infection?

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What constitutes a good immune response? Why do some HIV-infected people develop AIDS in months whilst others remain healthy for decades? How do your genes affect your outcome of infection? These are the fundamental questions that we are trying to answer. The size of the HIV pandemic is staggering. In some areas of sub-Saharan Africa 1 in every 3 adults are infected. A cheap effective vaccine is desperately needed. The first step in designing an HIV vaccine is understanding the type of immunity that it should induce, i.e. what exactly is a good immune response? Answering this question is complicated by the fact that HIV destroys immune cells. Consequently we cannot tell if immune response attributes associated with good viral control are a cause or an effect of low levels of virus. This means that many traditional methods of investigating the immune response are redundant. A clue as to what determines the efficacy of the human immune response lies in the observation that some people naturally control HIV infection much better than others and that this is, in part, related to the person’s genetic makeup. The aim of this project is to understand what a good immune response is by understanding why some genes result in better immune control than others. The research will be conducted by a novel mathematical analysis of existing HIV-infected patient databases. Our results will contribute to our understanding of what constitutes a good immune response. This could have direct implications for human health and HIV vaccine development. More generally, severity of illness for all 3 of the world’s most devastating diseases: AIDS, malaria and TB is partially determined by host genetics. We hope that the methods and insights our research generates will be applicable in all of these cases.