Duke Team Identifies a Strategy to Guide the Immune System to Respond to HIV
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DURHAM, N.C. – Highly specific HIV antibodies could be induced by vaccination using a new strategy developed by researchers at the Duke Human Vaccine Institute. Vaccination using this strategy may be able to counter the virus’s ability to outpace the immune system.
Publishing in Nature Communications, the researchers describe a strategy for engineering pieces of the HIV envelope that stimulate the immune system toward making protective antibodies.
“To achieve this, we have to find the right antibody and then guide it along the way toward key mutations that are really rare,” said senior author, Barton Haynes, M.D., director of the Duke Human Vaccine Institute. “What we have found is that the immune system does not want to make protective anti-HIV broadly neutralizing antibodies unless it receives some help. This study demonstrates that, with the help of computer simulations, we were able to find the right HIV envelope immunogens to guide the immune system to make the desired antibody types.”
Lead author Rory Henderson, Ph.D., used a computational technique called molecular dynamics simulation to identify how key antibody mutations prevent the virus from escaping neutralization.
Their strategy was based on genes for antibodies with known potential for broad HIV-1 neutralization. By monitoring how these antibodies recognize the virus at the atomic scale and with a time resolution of nanoseconds, they identified changes to features on the envelope that favored those key antibody mutations.
“A lot of work has been done with what we call priming -- getting that gene to start to express and start seeing the antigen,” Henderson said. “What we've never been able to do is coax it toward a specific mutation, which is what we would need for a vaccine. Our study showed how we can do that.”
Haynes said the finding moves HIV vaccine development closer to fruition by showing that the immune system can indeed be guided to produce antibodies with specific mutations that are needed for antibody function.
Overall, researchers project they will need to induce broadly neutralizing antibodies that bind to HIV at four different sites on the virus’s envelope. This work focuses on two such neutralizing antibody types.
In addition to Haynes and Henderson, study authors include Kara Anasti, Kartik Manne, Victoria Stalls, Carrie Saunders, Yishak Bililign, Ashliegh Williams, Pimthada Bubphamala, Maya Montani, Sangita Kachhap, Jingjing Li, Chuancang Jaing, Amanda Newman, Derek W. Cain, Xiaozhi Lu, Sravani Venkatayogi, Madison Berry, Kshitij Wagh, Bette Korber, Kevin O. Saunders, Ming Tian, Fred Alt, Kevin Wiehe, Priyamvada Acharya, and S. Munir Alam.
The study received funding support from the National Institute of Allergy and Infectious Diseases, which is part of the National Institutes of Health, through the Division
of AIDS Consortia for HIV/AIDS Vaccine Development (UM1AI144371, R01AI145687, U54AI170752, DP2-AI164323-03). A full list of supporters is provided in the study.