US researchers announced on Thursday the discovery of potent human antibodies that can stop 91 percent of HIV strains, though creating real-world applications will require much more work. "We're going to be at this for awhile," said Gary Nabel, the team's leader and the report's co-author, who is director of the Vaccine Research Center at the National Institute of Allergy and Infectious Diseases (NIAID).
The antibodies, called VRC01 and VRC02, were discovered in the blood of an HIV-positive African-American gay man known as Donor 45. The researchers developed a novel molecular device that honed in on specific cells that make antibodies against HIV.
While HIV's surface mutates, one place the virus does not change significantly is where it attaches to a particular molecule on the cells it infects. Located on the surface spikes HIV uses to attach to human immune cells and infect them is an area called the CD4 binding site. The antibodies VRC01 and VRC02 attach to the CD4 binding site, blocking the virus from grasping immune cells.
Until last year, only a few broadly neutralizing antibodies to HIV had been identified, and none worked against more than 40 percent of known HIV variants. More recently, efficient new antibody detection methods have fueled the discovery of a half dozen such antibodies, as documented in peer-reviewed journals. Most of the new antibodies are more potent and effective in lower concentrations than previous ones.
Donor 45's antibodies did not protect him from acquiring HIV, so he likely only produced them after infection. Of 25 million of his cells screened, just 12 produced the antibodies. And there is evidence it took months or even years for him to create the antibodies, meaning any vaccine might require repeated boosters or other ways to stimulate production.
The NIAID researchers also determined at the atomic level how VRC01 works when attaching to HIV. With this knowledge, they have begun designing candidate vaccine components that could make similar antibodies. The information also could help in other developments, such as antibody-boosted antiretroviral therapies, microbicides or gene therapy.
The reports, "Rational Design of Envelope Identifies Broadly Neutralizing Human Monoclonal Antibodies to HIV-1" and "Structural Basis for Broad and Potent Neutralization of HIV-1 by Antibody VRC01," were published in Science (2010;doi:10.1126/science.1187659 and doi:10.1126/science.1192819).
07/09/10
UNITED STATES: Advance in Quest for HIV Vaccine
Source: Wall Street Journal:: Mark Schoofs; Courtesy of the CDC National Center for HIV, STD, and TB Prevention