Discovery of antibodies boosts quest for AIDS vaccine
Published Thursday, July 8, 2010 6:28PM EDT
TORONTO - Researchers have discovered two powerful antibodies that neutralize most known strains of the AIDS virus in laboratory testing, providing a possible new direction for developing an effective vaccine to prevent the disease.
The naturally occurring antibodies, dubbed VRC01 and VRC02, were isolated from an individual with HIV who is known as a slow progressor -- he is infected with the virus but has remained essentially healthy.
"The antibodies work against about 90 per cent of all of the viruses we tested," said Dr. John Mascola, deputy director of the Vaccine Research Center, part of the U.S. National Institute of Allergy and Infectious Diseases (NIAID), which led the study.
The multicentre research team, whose work is published this week in the journal Science, tested about 200 different variations of the AIDS virus, collected from infected people around the globe.
"Each virus is different and that is one of the characteristics of HIV," Mascola said from Bethesda, Md. "It's a highly mutable virus and there are literally thousands and thousands of variants of the virus circulating throughout the world at any given time, and even variants in a single individual."
What has especially excited the researchers, however, is their discovery about how a VRC antibody works to stop HIV from entering and killing key immune system cells, called CD4 T-cells.
The antibodies work by attaching themselves to a site on the virus that allows it to take over these disease-fighting cells -- a site that has remained intact through countless mutations over the decades.
"The antibodies attach to a virtually unchanging part of the virus, and this explains why they can neutralize such an extraordinary range of HIV strains," said Mascola. "Antibodies like this are proof-of-concept that the human immune system can make very potent antibodies against HIV."
"And that's very important information for helping us design a vaccine."
There have been numerous attempts to develop an AIDS vaccine, but those efforts have been stymied so far because the virus mutates so quickly. For frustrated scientists, it's been akin to shooting at a moving target.
That's why, said Dr. Alan Bernstein, this discovery could be a "major breakthrough" in the quest for an AIDS vaccine.
"In a sense they have found at least one of the Achilles heels of the virus," Bernstein, executive director of the Global HIV Vaccine Enterprise, said Thursday from New York.
"This group of investigators have found it. And not only that, they've figured out how it works ... So the big push now is how do we turn that information into thinking about a vaccine."
He said the research adds to a number of other recent discoveries, including neutralizing antibodies reported on last September by the Scripps Research Institute, which have reinvigorated the hunt for an effective vaccine.
"So I think the mood in the field has really turned around and there's a sense that we're entering a new era in HIV vaccine research based on the kinds of exciting science that's now coming out," said Bernstein, former president of the Canadian Institutes of Health Research.
Mascola said his team has already begun to design components for a candidate vaccine that could teach the human immune system to make antibodies similar to VRC01 and VRC02 that might prevent infection by the vast majority of HIV strains worldwide.
Testing would begin in small lab animals, then in non-human primates like macaques that can become infected with a simian form of the virus. If the animal results are positive, the next step would be to test the vaccine in humans. Such a trial would likely not occur for two or three years, he said.
NIAID director Dr. Anthony Fauci said in a statement that the research should not only speed up efforts to find a preventive HIV vaccine, but "the technique the teams used to find the new antibodies represents a novel strategy that could be applied to vaccine design for many other infectious diseases."