In an advance for HIV vaccine research, scientists have for the first time determined how both the virus and a resulting strong antibody response co-evolved in one HIV-infected individual. The findings could help researchers identify which proteins to use in investigational vaccines to induce antibodies capable of preventing infection from an array of HIV strains. Previously, a study of antibody genetics enabled scientists to deduce the step-by-step evolution of certain broadly neutralizing antibodies--those that can prevent infection by the majority of HIV strains found around the globe. Yet the specific viruses that gave rise to those antibodies and the virus mutations that drove them to reach their final form remained unknown, hampering HIV vaccine discovery.
In the current study, scientists identified one of the roughly 20 percent of HIV-infected individuals who naturally develop broadly neutralizing antibodies to the virus after several years of infection. This person in Africa was a volunteer in a study in which participants gave weekly blood samples beginning early in the course of infection. This individual had joined the study just 4 weeks after infection and was followed for more than 3 years. Having blood samples from such an early stage enabled researchers to pinpoint the particular "founder" virus that triggered the immune system to make an immature broadly neutralizing antibody against HIV, as well as the cell from which that antibody emerged. Analyses of the weekly samples also enabled the scientists to see the series of changes that the virus and antibody underwent over 2.5 years until the antibody matured to a form capable of potently neutralizing the virus. Scientists are now attempting to create a vaccine that harmlessly mimics the virus at key points in the observed process to generate broadly neutralizing HIV antibodies, first in uninfected animals and then in uninfected people.
The study was led by Duke University's Center for HIV/AIDS Vaccine Immunology-Immunogen Discovery (CHAVI-ID), which is funded by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health. Scientists at NIAID's Vaccine Research Center (VRC) also played a central role, collaborating with researchers at the NIH Intramural Sequencing Center, administered by the NIH National Human Genome Research Institute, along with seven other institutions.
H. Liao et al. Co-evolution of a broadly neutralizing HIV-1 antibody and founder virus. Nature DOI: 10.1038/nature12053 (2013).
NIAID Director Anthony S. Fauci, M.D., and VRC Section Chief Peter D. Kwong, Ph.D., are available for comment.
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