“They essentially rescued the immune memory of six individuals infected with HIV into a test tube,” says Dennis Burton, an immunology professor at the Scripps Research Institute and head of the newly formed HIV Neutralizing Antibody Center. “It’s a major tour de force of immunology.” But he notes that while the study is a great leap forward, there’s still some distance to go before researchers completely understand how people’s immune systems respond to HIV. “There’s still many outstanding problems and issues–we’ve got some of the pieces of the jigsaw puzzle, but there’s a lot of pieces still missing,” Burton says.
Finding such a broad array of antibodies was a huge task that required a novel set of techniques. First, the researchers had to identify the immune cells that bound to gp140 by staining them with HIV proteins. Cells that tested positive were separated out, and the scientists created a “library” of the cells’ DNA fragments. From these fragments, they cloned all the antibodies, expressed them in a new batch of cells, purified out the secreted antibodies, then tested them for their ability to bind to gp140 and to determine whether they inhibited virus replication.
“It’s an impressive amount of work,” says David Montefiori, the director of the Laboratory for AIDS Vaccine Research and Development at Duke University Medical Center. “Nothing of this magnitude has even been attempted before.”
The newly isolated antibodies themselves are unlikely to be an effective protective treatment or therapy. While some of the 433 antibodies can neutralize some strains of HIV, taken together, they cannot broadly neutralize all relevant strains. And the virus would continue to mutate, likely rendering the antibodies’ neutralizing powers less potent over time.