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Study of antibody evolution charts course toward HIV vaccine

In an advance for research, a scientific team has discovered how the immune system makes a powerful antibody that blocks of cells by targeting a site on the virus called V1V2. Many researchers believe that if a vaccine could elicit potent antibodies to a specific conserved site in the V1V2 region, one of a handful of sites that remains constant on the fast-mutating virus, then the vaccine could protect people from . Analyses of the results of a clinical trial of the only experimental to date to have modest success in people suggest that antibodies to sites within V1V2 were protective1. The new findings point the way toward a potentially more effective vaccine that would generate V1V2-directed HIV .

The study was led by scientists from the National Institute of Allergy and Infectious Diseases (NIAID), part of the U.S. National Institutes of Health; Columbia University; the Centre for the AIDS Programme of Research in South Africa (CAPRISA); and the National Institute for Communicable Diseases, Johannesburg.

They began by identifying an HIV-infected volunteer in the CAPRISA2 cohort who naturally developed V1V2-directed HIV neutralizing antibodies, named CAP256-VRC26, after several months of infection. Using techniques similar to those employed in an earlier study of HIV-antibody co-evolution3, the researchers analyzed blood samples donated by the volunteer between 15 weeks and 4 years after becoming infected. This enabled the scientists to determine the genetic make-up of the original form of the antibody; to identify and define the structures of a number of the intermediate forms taken as the antibody mutated toward its fullest breadth and potency; and to describe the interplay between virus and antibody that fostered the maturation of CAP256-VRC26 to its final, most powerful HIV-fighting form.

Notably, the study revealed that after relatively few mutations, even the early intermediates of CAP256-VRC26 can neutralize a significant proportion of known HIV strains. This improves the chances that a V1V2-directed HIV vaccine developed based on the new findings would be effective, according to the scientists, who have begun work on a set of vaccine components designed to elicit V1V2 neutralizing antibodies and guide their maturation.

Source

1 RV144 Trial

2 CAPRISA

3 NIH Scientists, Grantees Map Possible Path to an HIV Vaccine, H. Liao et al. Co-evolution of a broadly neutralizing HIV-1 antibody and founder virus. Nature DOI: 10.1038/nature12053 (2013).

NA Doria-Rose et al. Developmental pathway for potent V1V2-directed HIV-neutralizing antibodies. Nature, published online 02 March 2014, DOI: 10.1038/nature13036

NIH/National Institute of Allergy and Infectious Diseases