Scientists have discovered how the immune system makes a powerful antibody that blocks HIV infection of cells by targeting a key site, paving way for an effective vaccine for the deadly virus.
Researchers believe that if a vaccine could elicit potent antibodies to a specific conserved site in the V1V2 region of the virus, one of a handful of sites that remains constant on the fast-mutating virus, then the vaccine could protect people from HIV infection.
Analyses of the results of a clinical trial of the only experimental HIV vaccine to date to have modest success in people suggest that antibodies to sites within V1V2 were protective.
The new findings point the way towards a potentially more effective vaccine that would generate V1V2-directed HIV neutralising antibodies, researchers said.
The study led by the National Institute of Allergy and Infectious Diseases (NIAID) scientists began by identifying an HIV-infected volunteer who naturally developed V1V2-directed HIV neutralising antibodies, named CAP256-VRC26, after several months of infection.
Using techniques similar to those employed in an earlier study of HIV-antibody co-evolution, the researchers analysed 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 towards its fullest breadth and potency.
It also allowed them to describe the interplay between virus and antibody that fostered the maturation of CAP256-VRC26 to its final, most powerful HIV fighting form.
The study showed that after relatively few mutations, even the early intermediates of CAP256-VRC26 can neutralise 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 scientists, who have begun work on a set of vaccine components designed to elicit V1V2 neutralising antibodies and guide their maturation.