Newly discovered broadly neutralizing antibodies appear to block HIV from entering and infecting human immune cells. These include two antibodies that thwart more than 90 percent of circulating HIV-1 strains, a discovery that may aid in the development of a vaccine.

VRC01 (green and blue) binding to the gp120 envelope glycoprotein (gray) and the HIV-1 site of vulnerability (red). Image courtesy of Peter Kwong, Jonathan Stuckey, Tongquing Zhou

The researcher team, composed mainly of scientists with the National Institutes of Health, reports the findings and details of a new method used to single out the antibodies from the blood of an HIV-positive patient using a specially designed glycoprotein probe on Science's website today (8th July).

The new antibody detection method "is an extraordinary hook that has allowed them to fish out antibodies that are unique and special," Munir Alam an immunologist at Duke University's Human Vaccine Institute who was not involved with the study, told The Scientist. "Previously we had missed all these antibodies because we were not able to fish them out."

The antibodies -- dubbed VRC01, VRC02, and VRC03 after the NIH's Vaccine Research Center (VRC), where the research took place -- prohibit HIV's entry into immune cells by occupying a site on the virus's envelope that binds to the CD4 receptor on the surface of T cells and other immune cells. Most HIV virus strains rely on this site -- occupied by an envelope glycoprotein called gp120 -- to bind to the CD4 receptor and gain access to immune cells. "Although the virus can hide many things and evade the immune system, one of the things it can't change is that structure on its envelope that binds the CD4," explained Gary Nabel, director of the VRC and senior author on the paper.

Because the structure of the gp120 protein is conserved across many different HIV-1 strains, a vaccine that stimulates production of the antibodies that bind to it could potentially confer protection against infection in HIV-negative people.

Having such a specific and vulnerable target on HIV's surface is a major advance, Nabel told The Scientist. "It's the difference between having a GPS in your car and driving around in the dark with no map," he said. "Now we suddenly have this very high level of definition of the target and ways of directing ourselves to where we want to go."

"Clearly if we could elicit this response in people who are naive to HIV infection, it would be very exciting," agreed Rick King, vice president of vaccine design at the International AIDS Vaccine Initiative (IAVI). "I think that it's an exciting time right now in the HIV vaccine field."

The new antibodies bear some resemblance to a couple of broadly neutralizing antibodies -- PG16 and PG9 -- that IAVI researchers, in collaboration with scientists from other institutions, discovered last year, added King, who did not participate in the most recent research. "They bind to different sites, but they're both very potent, and they're both very broad in terms of recognition of different HIV isolates," he said. Both sets of findings are "really giving us some additional tools with which to design vaccines and to identify how we can make immunogens."

A companion study that solves the crystal structure of VRC01 bound to HIV and gives a clear picture of the interaction between the two molecules was also published today on Science's website.

Nabel added that his group is now beginning work on developing an HIV vaccine based on the new data. "We've made some good progress. We're certainly farther along than we were a year ago," he said. "I'm optimistic that we can get where we need to go."

But it won't be easy. For one, the newly discovered antibodies mature in the human body slowly by a process called somatic diversification, in which B cells, which produce antibodies, home in on specific parts of a pathogen and then mutate so specific antibodies can more strongly bind to the pathogen. "How do we make this process happen efficiently?" Nabel asked. Adjuvants or other complementary antibodies, such as PG16 and PG9, may help increase this efficiency. "That's all part of the future work we need to do."

X. Wu, et al., "Rational Design of Envelope Surface Identifies Broadly Neutralizing Human Monoclonal Antibodies to HIV-1," Science, published online 8 July 2010, doi: 10.1126/science.1187659.

T. Zhou, et al., "Structural Basis for Broad and Potent Neutralization of HIV-1 by Antibody VRC01," Science, published online 8 July 2010, doi: 10.1126/science.1192819.


Related stories:

More hope for genetic fix for HIV
[16th June 2010]

Math explains HIV immunity
[5th May 2010]

HIV antibody duds explained
[19th November 2009]