NEW YORK (Reuters Health) – In those relatively rare “slow-progressing” HIV-infected patients who mount an effective immune response to the infection, the neutralizing activity is made up of multiple antibodies targeting different epitopes on the major viral surface protein gp120, rather than one antibody having particularly strong activity, new research shows.

This finding could have important implications for the development of a vaccine to combat HIV, the researchers emphasize.

Their study, reported online March 15th in Nature, is not the first to identify high levels of neutralizing antibodies in the serum of slow progressors. The specificity and activity of these antibodies, however, was unclear.

To investigate, Dr. Michel Nussenzweig, from The Rockefeller University, New York, and co-researchers cloned 502 antibodies from HIV envelope-binding memory B cells taken from six patients with broadly neutralizing antibodies and low to intermediate HIV levels.

The team found that the B-cell memory response to gp140 (a combination of gp120 and gp41) consisted of up to 50 different clones that produce high-affinity antibodies against various epitopes of gp120, including the variable loops, the CD4-binding site, and the co-receptor-binding site. In addition, the researchers identified a new neutralizing epitope that was in the same area as the CD4-binding site.

“Our results do not rule out the possibility that broad neutralizing activity in serum can be the result of a single highly effective antibody, and the goal of eliciting such antibodies by vaccination remains important,” the authors state.

“However,” they conclude, “the data suggest that a vaccine that phenocopies the natural anti-HIV immune response in patients with broadly neutralizing serological activity and elicits a combination of antibodies might also be an effective means of protection against a large number or HIV strains.”

Reference:
Nature 2009.