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Potent HIV Antibodies Spark Vaccine Hopes
 
 
  Download pdf of full investigator report attached
 
Jon Cohen
Science 4 September 2009
 
If HIV/AIDS researchers had a wish list, at the very top would sit a vaccine that could teach the body to make potent antibodies against the many strains of the virus. Despite 25 years of effort, no such vaccine is in sight, but now they are a step closer. A large team of researchers has identified the most powerful, broad-acting antibodies yet against multiple strains of the virus.
 
Finding good antibodies is a far cry from developing a vaccine that prods the immune system to produce them. But "broadly neutralizing antibodies" (bNAbs) are rare: Researchers have identified only a half-dozen to date. Now an international group funded mainly by the International AIDS Vaccine Initiative (IAVI) has discovered two new ones that have an unusual potency. "This has actually made me quite optimistic-for once," says Dennis Burton, an immunologist at the Scripps Research Institute in San Diego, California, who led the research effort.
 
For many years, Burton says, he thought that if an antibody had a broader reach, it inevitably would be weaker. "I wondered whether there would be any antibody better than the ones we had," he says. "Well, these are."
 
Burton, his graduate student Laura Walker, and 33 other researchers report online 3 September in Science pdf attached (www.sciencemag.org/cgi/content/abstract/1178746) that the two new antibodies have unusual characteristics that open new avenues of AIDS vaccine research. "It's a great paper that describes very novel antibodies," says immunologist John Mascola of the Vaccine Research Center at the National Institute of Allergy and Infectious Diseases in Bethesda, Maryland.
 
The researchers first collected blood from some 1800 HIV-infected people in Africa, Asia, Europe, and North America. Using novel techniques, they identified 10% who had antibodies that could derail more than a dozen different strains of the virus. This paper focuses on one sub-Saharan African donor; the person did not benefit appreciably from the antibodies, which are no match for HIV once an infection is established.
 
The researchers sifted through a staggering 30,000 antibody-producing B cells from the donor and isolated two monoclonal antibodies, dubbed PG9 and PG16, that could prevent infection in more than 70% of 162 viral strains tested in cell culture. Not only were they broad acting, but the antibodies worked at minute levels-a magnitude lower than the four best characterized bNAbs so far. "It's an enormous amount of work-a tour de force," says AIDS vaccine researcher Ronald Desrosiers, head of the New England Primate Research Center in Southborough, Massachusetts.
 
Figure 1

HIV-1.gif

It takes three. Newly discovered, highly potent antibodies (red) that block infection with many HIV strains bind to trimers (blue mesh) on the viral surface.
 
On a more sobering note, many researchers have tried to make vaccines that elicit previously identified bNAbs. "In the last 5 years, there have been intensive efforts, and no one has succeeded," Burton says.
 
Still, Burton and others hope that understanding the unusual way that PG9 and PG16 stop the virus will provide new leads for AIDS vaccine designers. Specifically, HIV's surface proteins attach to immune cells to establish infections. The surface proteins naturally occur in clusters of three, or trimers, and PG9 and PG16 work only against the trimer. Other bNAbs bind to trimers as well as single surface proteins, or monomers. So this suggests that if a vaccine can present the surface proteins to the immune system in the trimeric form, it may have extra punch. It might also help explain why several AIDS vaccines that contain monomeric surface proteins have performed poorly.
 
Wayne Koff, who heads research and development at IAVI, says PG9 and PG16 are the first of several new bNAbs that he predicts will help guide the field. In particular, researchers hope the antibodies might help crystallographers finally elucidate the structure of a trimer, which occupies another slot on the wish list. "The machine is built and ready to crank out a lot more-and it's very likely to," says Koff.
 
 
 
 
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