DUKE (US) — For the first time, researchers describe the co-evolution of antibodies and virus in a person with HIV whose immune system mounted a broad attack against the pathogen.
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, leading to an arms race that the virus usually wins.
The current research, published in Nature, was aided by new technologies that can detect early infection and track the subsequent immune response and virus evolution. It fills gaps in knowledge that have impeded development of an effective vaccine for a virus that has killed more than 30 million people worldwide.
“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,” says Barton F. Haynes, director of the Human Vaccine Institute at Duke University.
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. The individual also exhibited a fortuitous trait that occurs in only about 20 percent 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, researchers 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,” Haynes says. “This is a process of discovery and we’ve come a long way with regard to understanding what the problem has been.”
Researchers from the Boston University, Stanford University, Columbia University, University of North Carolina, and the University of Pennsylvania contributed to the study, which was funded in part by the National Institutes of Health and the Center for Vaccine Immunology-Immunogen Discovery.
Source: Duke University