How to Hit HIV Where It Hurts

Immunology Interest Group Seminar Series No medical procedure has saved more lives than vaccination. But, today, some pathogens have evolved which have defied successful vaccination using the empirical paradigms pioneered by Pasteur and Jenner. One characteristic of many pathogens for which successful vaccines do not exist is that they present themselves in various guises. HIV is an extreme example because of its high mutability. This highly mutable virus can evade natural or vaccine induced immune responses, often by mutating at multiple sites linked by compensatory interactions. I will first describe how by bringing to together concepts from the physical sciences with in vitro experiments and clinical data the “ fitness landscape ” of HIV has been defined with explicit account for collective mutational pathways, how this knowledge has been harnessed for immunogen design, and what are the current challenges. I will next describe how research at the intersection of immunology, evolutionary biology, and physics is revealing how affinity maturation occurs in the presence of multiple variant antigens, and how the results can inform the design of vaccination protocols that may be able to induce broadly neutralizing antibodies against highly mutable pathogens (e.g., HIV). Arup K. Chakraborty is the Robert T. Haslam Professor of Chemical Engineering, Physics, Chemistry, and Biological Engineering at MIT. He is the founding Director of MIT ’ s Institute for Medical Engineering...
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