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Research

To date there is no effective vaccine against HIV infection, and yet a safe and efficacious vaccine is the best and most economical means of curbing the global HIV/AIDS pandemic.  A vaccine typically trains the human immune system to make protective antibodies against a particular virus or pathogen. In the case of HIV, it has been extremely difficult to train the human immune system (or even that of an animal) to make protective (or neutralizing) antibodies using conventional approaches. We are studying this problem at the molecular level to help advance vaccine development. Antibodies with an extraordinary ability to block HIV-1 infection have been described. These can neutralize a wide range of different HIV-1 isolates found around the globe by binding to the envelope glycoprotein spikes (Env). We are studying the molecular features of these antibodies as well as the functional stability, molecular heterogeneity, antigenicity and immunogenicity of HIV-1 Env. Analysis of particular antibody specificities and how each recognizes different Envs and Env mutants on a case by case basis, we can understand their mechanism of action, identify weaknesses in HIV Env, and rationally modify Env molecules. We can then screen for Env vaccine leads that target these weaknesses and attempt to enhance the immune (antibody) response to HIV in animal models.

Our research interests are in HIV-1 pathogenesis, therapy and vaccine design, as well as molecular immunology and host-pathogen interactions. Some of our research entails monoclonal antibody discovery, determining mechanisms of activity of anti-HIV-1 antibodies and fusion inhibitors, and studying HIV-1 envelope protein structure-function. We have identified and characterized a number of recombinant antibody fragments (IgGs, Fabs and single-chain Fvs) against the HIV-1 envelope proteins, gp120 and gp41, using phage display and single B cell sorting. We have identified a conserved region on the ectodomain of gp41 that is proximal to the membrane-spanning domain and the target of broadly neutralizing antibodies (i.e. MPER). We are investigating the MPER and other targets on HIV-1 gp41 (and gp120) as targets for vaccine development. We have also immunized mice, rabbits and rhesus macaques with HIV-1 peptides and proteins that have been designed using our molecular characterizations, and are making improvements to these immunogens in an effort to elicit broadly neutralizing antibodies.

Using innovative approaches and techniques, and by generating novel molecular tools, we aim to identify vaccine leads that can be developed and/or incorporated into an effective HIV vaccine.