My laboratory is currently working in three areas: 1) identification of the immune correlates of protection from infection by the human immunodeficiency virus (HIV) 2) characterization of changes in HIV-specific immune responses that occur early in primary HIV infection and 3) evaluation of hepatitis C virus (HCV)-specific immunity in persons who exhibit different disease courses. These research themes are all related by their application to the design of vaccines for HIV and HCV.
1) Correlates of protection from HIV infection Our laboratory studies populations of individuals at who, despite being at high risk for HIV infection, remain uninfected. These include persons exposed to HIV either sexually or intravenously. A persistent uninfected status in the face of long-term high-risk behavior could be due to natural resistance to HIV. Work is ongoing towards elucidating the potential mechanisms for natural resistance by concentrating on acquired HIV-specific immunity. Our investigations to date support the current trend in HIV vaccine design, which is to develop vaccines that induce cellular HIV-specific responses. Current projects include screening exposed uninfected persons for immune recognition of all expressed HIV genes and comparing recognition specificity in this population with that in HIV infected persons. Our laboratory is also investigating CD4+ T cell immunity in this population. The components of protective immunity will be studied in an animal model.
2) HIV-specific immunity in primary infection. Virus-specific immune responses occurring early in infection are believed to determine the subsequent course of HIV infection, i.e. how rapidly an individual will progress to acquired immunodeficiency (AIDS). The goal of this research theme is to understand the dynamics of changes in HIV-specific CD4+ and CD8+ T cell responses in early infection and how introduction of treatment for HIV soon after infection affects disease progression. In the absence of a cure for HIV infection, our goal is to define ways of manipulating the immune system so as to favor a disease course similar to that of a subpopulation of HIV infected persons called long-term non-progressors. Long-term non-progressors represent approximately 5% of HIV infected persons. They are able to control plasma virus levels and maintain high CD4 counts without treatment for years without developing AIDS.
3) HCV-specific immunity Approximately 70% of intravenous drug users in the Montreal area are HCV infected. Of those who are not infected with this virus and who actively share needles, a subset has been infected and cleared the virus and a second subset may be naturally resistant to the virus. Our laboratory is comparing immune response to HCV among these three populations with the goal of identifying immunity associated with viral clearance or resistance versus establishment of chronic infection.