A Molecular Arms Race: HIV versus the Immune System

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Over 30 years after the emergence of HIV-1, there is no effective vaccine, and AIDS remains an important threat to global public health. Following infection by HIV-1, the host immune response is unable to clear the virus due to a variety of factors, including rapid viral mutation and the establishment of latent reservoirs. The only target of neutralizing antibodies is the trimeric envelope spike complex, but HIV-1 can usually evade anti-spike antibodies due to rapid mutation of its two spike glycoproteins. We use structural biology, biochemistry, and biophysical methods to characterize antibody recognition of the HIV-1 Env spike, with the goal of using structural knowledge to design immunogens that can elicit broadly neutralizing antibodies. We also use structure-based protein design methods to engineer antibodies that can resist some of the common routes of HIV-1 mutation, with the hope that the designed antibodies could be used in passive immunotherapy methods for HIV-1 treatment and/or prevention.

Pamela J. Bjorkman, PhD, David Baltimore Professor of Biology & Bioengineering, Caltech

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