New Research Points to New Route for Developing HIV Vaccine

By tracking the earliest days of one person’s robust immune response to HIV, researchers at Duke and the NIH Vaccine Research Center have begun to chart a new route for developing a vaccine that may boost the body’s ability to neutralize the virus.
The research team, led by Barton F. Haynes, MD, director of the Duke Human Vaccine Institute, and John Mascola, MD, acting director of the NIH Vaccine Research Center, have for the first time described the co-evolution of antibodies and virus in a person with HIV whose immune system mounted a broad attack against the pathogen. Their findings were published April 3, 2013, in the journal Nature.
Most vaccines work by inducing this antibody response, but the HIV virus has proved to be a difficult vaccine target. When HIV antibodies are produced, they typically have a limited range, and the virus changes rapidly to escape harm.
The current research was aided by new technologies that can detect early infection and track the subsequent immune response and virus evolution.
“This project could only have been carried out by a multidisciplinary team working closely together,” said Dr. Haynes, who led the work as a project of the Duke Center for HIV/AIDS Vaccine Immunology-Immunogen Discovery (CHAVI-ID) consortium, which is funded by the National Institute of Allergy and Infectious Diseases. “For the first time, we have mapped not only the evolutionary pathway of the antibody, but also the evolutionary pathway of the virus, defining the sequence of events involved that induce the broadly neutralizing antibodies.”
The key to this finding was a person in Africa whose HIV infection was detected so early that the virus had not yet mutated to avoid the immune assault. This person also exhibited a trait that occurs in only about 20% of people infected with HIV – an immune system that produces broadly neutralizing antibodies. These immune weapons attack vulnerable sites of the virus that are conserved despite mutations. In identifying the early viral infection, the team found the outer envelope, the viral surface glycoprotein, which triggered the start of the broadly neutralizing antibody development.
By tracking the precise virus and antibody pathways involved, the Duke CHAVI-ID and NIH teams now have a detailed road map for development of a potential vaccine, which involves immunogens with an outer envelope specifically selected to stimulate the production of broadly neutralizing antibodies.
“The next step is to use that information to make sequential viral envelopes and test them as experimental vaccines,” Dr. Haynes said. “This is a process of discovery and we’ve come a long way with regard to understanding what the problem has been.”