Virology and Immunology
The development of a safe, affordable and efficacious HIV-1 vaccine is perhaps the defining scientific challenge of our time. Rational vaccine design will require a better understanding of immune correlates of HIV-1 protection or control. Our laboratory is interested in identifying the possible correlates of protection against infection among exposed seronegative persons and correlates of viral control during HIV-1 infection. We also aim to understand why certain individuals achieve long-term viral control without antiretroviral therapy intervention and why the viral load set point differs significantly among infected people. Naturally resistant or infected individuals who achieve durable viral control may hold the key to vaccine development or novel immunotherapies.
Viral control or lack of control may depend on the complex interplay between host and viral factors. Therefore, our laboratory focuses on understanding the interaction between the host and the virus and the underlying biological mechanisms that may explain why there is such heterogeneity in clinical outcome following exposure to or infection with HIV. The most significant genetic correlate of HIV control is human leukocyte antigen (HLA) class I type. HLA class I molecules are involved in viral antigen presentation to cytotoxic T lymphocytes (CTLs). We are interested in unraveling HLA-mediated mechanisms of viral control. We study cytotoxic T lymphocyte responses, their viral targets, their specificity and characteristics that determine their effectiveness in viral control. We also aim to understand why certain CTL responses are ineffective than others in suppressing virus replication and why the body is sometimes unable to mount detectable immune responses to some viral epitopes despite the presence of wild-type virus sequences that should induce an immune response based on patterns of responses seen in chronically infected persons. We also aim to understand how the virus responds and adapts to immune pressure, ultimately overcoming host immune defenses.
We also study the role of innate immunity in protection or control of HIV-1 infection. There is very limited understanding of the earliest immune defenses that the body mounts against HIV. Therefore, our laboratory aims to help elucidate the role and mechanisms of innate immunity in antiviral activity, effectiveness in vivo and the possible clinical benefit associated with these responses. We are also interested in understanding how innate immune responses shape subsequent adaptive immune responses, synergism between different arms of the immune system and viral adaptation or dysregulation of these immune responses. We aim to understand whether innate immune responses can be harnessed in prophylactic or therapeutic strategies against HIV. Our laboratory is also studying the immunopathogenesis and immunodiagnosis of tuberculosis, as a result of the resurgence of this disease in countries already heavily burdened by HIV/AIDS.
Ultimately, we hope to gain a more in-depth understanding of anti-HIV immune responses, immune escape and dysfunction pathways, and functional consequences for the virus from the earliest stages of infection. We hope that through these studies we can define the precise balance of immune responses and viral fitness required to achieve and maintain effective viral control. Considering the challenges experienced so far in the development of an effective HIV vaccine, we believe in vigorously pursuing promising avenues of vaccine design while exploring unconventional ideas that have not previously been widely studied, especially in human populations most severely affected by HIV/AIDS. We also have a special interest in developing a critical mass and building capacity for biomedical research in Africa.