Breakthrough in the Quest for an AIDS Vaccine

Professor Dennis Burton, Ph.D.

HIV's elusiveness lies in its constantly changing nature. The virus, which leads to AIDS, changes so often that a single person is in fact infected with many thousands of slightly different versions. The immune system has difficulty fighting so many variations.

"It's the most variable of viruses," says Dennis Burton, Scripps Research professor of immunology and microbial science and director of the Neutralizing Antibody Center. "It has evolved the most tricks to avoid detection and destruction."

The immune system puts up a fight, though. And in some rare cases it is able to produce a type of antibody that can battle more than one version of the virus.

These antibodies, called broadly neutralizing antibodies, are incredibly rare. No more than five had been discovered in the past decade. Which is why the September announcement that Scripps Research and International AIDS Vaccine Initiative investigators had identified two new broadly neutralizing antibodies was met with elation by the AIDS community and researchers alike.

Even more exciting is the fact that these new antibodies attack HIV on a part of the virus that doesn't mutate much.

"It looks like (they) target a particular region on the tops of these surface spikes that stud the viral surface," says Burton. "These spikes are important to the virus because it uses them to interact or bind to target cells."

Scientists think these spikes may prove to be the virus's Achilles heel.

Burton says an effective vaccine against AIDS will almost certainly induce antibodies like these.

"We still have a long way to go," says Burton. "But it is a very encouraging start."

It's a start that was made possible by Scripps Research's signature combination: world-class scientists plus cutting-edge technology plus well-designed partnerships.

Working through the Neutralizing Antibody Center, a partnership between Scripps Research and the International AIDS Vaccine Initiative (IAVI), the team set out to search systematically for broadly neutralizing antibodies. First, IAVI researchers collected blood samples from 1,800 HIV-infected individuals in sub-Saharan Africa. The samples were then passed to a team of investigators from Scripps Research and International AIDS Vaccine Initiative, which worked with a Seattle-based biotechnology company to troll through the thousands of samples and home in on those with the most effective antibodies.

Focusing on those samples, the team then turned to a San Francisco-based biotechnology company whose high-throughput technology allowed the researchers to pinpoint the most effective antibodies in those blood samples.

Then, drawing on Scripps Research's experts across disciplines, the team painted the picture of how these antibodies attack the virus.

The success story has received much attention around the world, but Burton took special joy in sharing it with two special groups last month.

On September 24, Burton and IAVI President Seth Berkley spoke to a small group of San Diego-area community leaders at the home of Gary and Carol Coburn as part of an effort to get local residents involved with the successes taking place in their backyard.

And just before that, Burton and Berkley told the story... this time to 100 international AIDS researchers who gathered at The Scripps Research Institute to discuss the vaccine possibilities of broadly neutralizing antibodies.

"When IAVI in 2002 started a consortium called Neutralizing Antibody Consortium, most of the effort in HIV vaccines was focused on cellular immunity," Burton says. Vaccines based on cellular immunity fight the virus by killing infected cells.

Burton credits IAVI for investing in neutralizing antibody research early on. "Even as long ago as 2002, IAVI recognized that we would need a component of an HIV vaccine that induced antibodies," he explains, emphasizing that an effective AIDS vaccine will likely require a combination of the two approaches.

The consortium, which has grown five-fold in the past seven years, last year partnered with Scripps Research to build a core concentration of researchers.

"I think what makes Scripps Research a good fit is that it is a real center for at least three of the important strands of this effort: immunology, virology, and structural biology," Burton says.

These strengths position the team well for its next step: finding immunogens – the active ingredients of vaccines.

"It's a great achievement for the institute if we can translate some of this vast knowledge and strength into something that would benefit such a large number of people," Burton says.

But it is no small undertaking. Your support can give Scripps Research's investigators the tools they need to turn these exciting findings into medical answers.