MIT researchers and colleagues are harnessing the power of multiple disciplines—from cutting-edge biology to physics, engineering, and computer science—to tackle one of the world’s great scourges: HIV, the virus that causes AIDS. Their ultimate goal, toward which they’ve made progress, is a vaccine against the disease.

HIV is difficult to combat because it can quickly mutate to evade the body’s immune response. As soon as the immune system recognizes the virus and begins to attack it, the virus changes, thus avoiding detection.

As a result, “designing a vaccination strategy for HIV is very hard because you must produce an immune response that HIV cannot mutate around.” That’s why, 30 plus years after the virus’s discovery, there is still no vaccine, says Arup Chakraborty, the Robert T. Haslam Professor of Chemical Engineering, Chemistry, Physics, and Biological Engineering and director of MIT’s Institute for Medical Engineering and Science (IMES).

Chakraborty approaches the challenge of creating such a vaccine from a unique perspective: he applies computational and theoretical techniques developed in the physical sciences to questions in immunology. Specifically, he and colleagues use these techniques, coupled with the power of genetic sequencing and computation, to define the mutational vulnerabilities of HIV. The goal, explains Chakraborty, is to figure out “where can you target HIV with an immune response so that if it tries to mutate to evade detection, it becomes less fit, hurting its ability to survive.” In other words, the idea is to corner the virus, forcing it either to be detected—and destroyed—by the immune system, or to mutate into a form that makes it weaker and less capable of reproduction.

The approach is bringing results, says Chakraborty, who is a founding member of the Ragon Institute of Massachusetts General Hospital, MIT, and Harvard; his colleagues in this work are all associated with the Ragon Institute. The team has identified an immunogen, or active component of a vaccine, made of protein fragments, or peptides, that could induce multiple mutations in the virus that would make it less fit.

Peptide-based vaccines, however, are difficult to deliver to the immune cells. So Chakraborty and his key clinician- scientist collaborator, Bruce Walker, MD, director of the Ragon Institute, joined forces with Darrell Irvine, a professor in the Koch Institute for Integrative Cancer Research, the Department of Biological Engineering, the Department of Materials Science and Engineering, and a founding member of the Ragon Institute. Irvine is a specialist in creating carriers for vaccines. He, in turn, linked the peptides to a lipid that causes them to bind to a protein called albumin. Albumin naturally travels to the lymph nodes, or the tissues where an immune response is induced. “We designed vaccines that hitchhike on albumin to get to where they need to be,” says Irvine.

Walker, who is also a professor at Harvard Medical School and one of the world’s experts on HIV, says, “It’s been exhilarating to work together with colleagues on this really big problem.” To date, he sums up, “we’ve identified vulnerable regions of the virus to target; we’ve made an immunogen based on that; and we’ve started to test it in non-human primates. Ultimately we hope to take this into human clinical trials.”

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