David Evans, PhD
Department of Microbiology and Molecular Genetics, Harvard Medical School
HIV infection and AIDS vaccine development
Investigate new approaches for AIDS vaccine development using SIV infection of non-human primates as a model system.
New therapeutic approaches to developing an AIDS vaccine; new strategies for blocking the mother-to-child transmission of HIV.
A more complete understanding of HIV biology is a prerequisite for further efforts aimed at creating an effective AIDS vaccine. Dr. Evans is exploring important aspects of SIV infection of non-human primates, the only bona fide in vivo model for studying HIV infection, to overcome obstacles to the development of an AIDS vaccine. His lab’s molecular studies on single-cycle SIV (scSIV) are yielding insights into the viral determinants and cellular tropism that define viral infectivity, and should lead to important hypotheses concerning novel routes for vaccine development. The lab has a particular expertise in cellular immunology, and is applying this knowledge to address the complex responses of host immune cells to HIV/SIV infection, including the notorious ability of HIV/SIV to evade the immune system. These studies will complement the scSIV experiments, and should help produce an in-depth understanding of HIV/SIV biology and the host’s response to HIV/SIV infection. Improved understanding of HIV/SIV biology and responses to infection will set the stage for new approaches to an AIDS vaccine that would be suitable for commercial development.
Current Research Interests
Dr. Evans is interested in understanding the HIV infection pathogenesis, and using that knowledge to facilitate new approaches to AIDS vaccine development. His laboratory uses non-human primate models infected with SIV as a surrogate for studying HIV infections in humans. Based on recent disappointing clinical study results, an effective AIDS vaccine may be years away. New insights into HIV’s biology are urgently needed. Dr. Evans’ lab is trying to uncover basic molecular and immunological mechanisms of HIV/SIV, while concomitantly exploring innovative strategies for pursuing HIV vaccine development.
- Study different methods for producing an HIV vaccine, including a vaccine modeled after single-cycle SIV (scSIV).
- Compare live attenuated SIV infection with scSIV infection for promoting immune protection against SIV.
- Research the phenomenon of mother-to-child transmission of HIV/SIV. The virus can be passed through breast feeding, but the target cells for the virus are not well-understood.
- Conduct experiments to address the role of immune cells, such as NK cells, in HIV/SIV pathogenesis.
- Investigate the suppression of histocompatibility complex class I molecules by SIV and its relationship to immune evasion.
Dr. Evans uses non-human primates as a model to study HIV infections and AIDS. His lab has pioneered the use of single-cycle simian immunodeficiency virus (scSIV), a genetically altered version of SIV that is restricted in its replicative ability to one round of infection. This modified virion is an excellent construct for investigating the biology of AIDS, and may be useful for devising a vaccine. In a recent animal study, Dr. Evans used the scSIV viral strain to improve the understanding of scSIV’s functional implications for envelope protein heterogeneity. The lab modified the scSIV moiety to contain different envelope glycoprotein versions, administered the different scSIV forms to monkeys, and measured the viral load for each envelope variant. The lab found that the removal of the cytoplasmic tail of the envelope glycoprotein uniformly elevated the plasma virus load in each construct. However, plasma clearance of the variants displayed marked differences, suggesting that envelope heterogeneity has important ramifications for viral infectivity.
Other recent work has centered on immune evasion by SIV/HIV, a key survival trait of lentiviruses. The lab demonstrated that the SIV Nef gene, as previously shown for HIV, is capable of diminishing the cell surface expression of a subset of major histocompatibility complex (MHC) class I orthologues in two monkey species. These data demonstrated an important conservation of function in Nef alleles encoded by HIV and SIV. The SIV-Nef’s selective downregulation of MHC class I molecules demonstrates the critical need for these lentiviruses to prevent the cytotoxic action of T-cells and NK cells.