[LINK] "Souped-up antibody fends off HIV"

[rfmcdonald]

This news item caught my attention. As usual, Nature--specifically, nature.com--had the most comprehensive article.

Although several antibodies against HIV-1 have previously shown promise, they were often structurally unusual in ways that confound vaccine designers. One region of an antibody might be unusually long, or contain a certain chemical modification — features that researchers do not know how to generate in the body using a vaccine.

"Antibodies are like people: every single one is unusual in its own specific way," says Peter Kwong, a structural biologist at the Vaccine Research Center, and a co-author on both papers. "These antibodies are freaks of nature."

In seeking better antibodies against HIV-1, Nabel, Kwong and their colleagues confronted another challenge: antibodies that broadly neutralize against HIV-1 are extremely rare. Kwong compares the search to looking for diamonds in a pile of cubic zirconia: "If you're simply picking up pretty rocks, you'll never find them," he says.

Instead, the team designed a probe to specifically pick out antibodies that act against the part of the virus's protein envelope that interacts with the cells targeted by HIV, called CD4+ cells. Other regions of the envelope that might stimulate an immune response were masked by replacing them with sequences from other viruses to reduce the odds of fishing out unwanted antibodies1.

The team screened 25 million antibody-producing white blood cells, called B cells, from 15 people with HIV-1, searching for those that bound to their probe. Only 29 cells fit the bill. From those, the researchers isolated three broadly neutralizing antibodies.

[. . .]

A vaccine based on this work would have to stimulate the body to produce antibodies like VRC01. At present, researchers do not fully understand how this maturation process works, making it difficult to design a vaccine that would harness it appropriately. Nabel speculates that such a vaccine may need to be given repeatedly, to foster the production of more mature, heavily mutated antibodies, and could even consist of different components at different stages — one given to stimulate the generation of the basic VRC01 backbone, and another administered later to select a specific 'mature' form of the antibody.