DURHAM, N.C. – Researchers at the Duke Human Vaccine Institute successfully created an HIV vaccine candidate that guides key immune cells along an evolutionary pathway to become broadly neutralizing antibodies.

In studies using mice, the immunogen activates diverse precursors of a specific broadly neutralizing antibody (bnAb) and starts the maturation of these antibodies at high enough levels to be a viable component of an HIV vaccine.

“A successful vaccine will need to induce lot of antibodies that target key regions of the virus, so these results are just one part of that goal, but a promising step,” said Mihai L. Azoitei, Ph.D., associate professor in the Duke Human Vaccine Institute and the Department of Cell Biology at Duke and lead author of a study featured on the cover of the journal Science Translational Medicine.

Azoitei and colleagues, building on a previous version of the immunogen developed at the Duke Human Vaccine Institute, aimed to increase the frequency of the mutations triggered by the immunogen.

They used computational modeling and structural analysis to enhance the immunogen’s ability to activate diverse bnAb precursors and to acquire the rare mutations that lead to bnAbs.

The resulting immunogen activated diverse precursors of an HIV V3-glycan bnAb – antibodies that target a key site of vulnerability on the outer envelope of the virus -- and promote their acquisition of a functionally critical mutation.

The immunogen was validated biochemically, structurally, and in three different humanized mouse models that were designed to evaluate HIV vaccine candidates.

“These results provide a blueprint for rationally designing vaccine candidates that engage different immune cells and guide them on the path to producing protective antibodies against HIV,” Azoitei said.

Further tests in primates and humans are planned.

In addition to Azoitei, study authors include Olivia M. Swanson, Qianyi E. Zhang, Elizabeth Van Itallie, Ming Tian, Alecia R. Brown, Caitlin Harris, A. Brenda Kapingidza, Brianna Rhodes, Lena M. Smith, Sravani Venkatayogi, Kenneth Cronin, McKenzie Frazier, Rob Parks, Maggie Bar, Chuancang Jiang, Joshua S. Martin Beem, Hwei-Ling Cheng, Jillian Davis,

Kelly McGovern, Amanda Newman, RJ Edwards, Derek Cain, S. Munir Alam, Kevin Wiehe, Kevin O. Saunders, Priyamvada Acharya, Fred Alt, and Barton F. Haynes.

The study received funding support from the National Institute of Allergy and Infectious Diseases of the National Institute of Health (UM1AI144371, U54AI170752, R01AI155804).