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After 25 Years, AIDS Vaccine Research Makes Mid-course Correction

BY Admin  April 8, 2008 at 6:30 PM EST

Syringe: AP file photo

“We’re at the middle of the road,” said Mitchell Warren, executive director of the AIDS Vaccine Advocacy Coalition. “We’re maybe two-thirds, maybe one-third of the way there.”

Still, researchers find it hard not be discouraged by recent developments. In September, in a huge blow to the field, officials from the pharmaceutical firm Merck announced that their once-promising vaccine candidate had not only failed when tested on humans, but seemed to increase the risk of contracting the deadly virus. Trials were halted.

And last month, a panel of top AIDS experts and government officials announced that the focus of vaccine research funding would be shifted away from large human trials and toward basic science: developing better animal models, studying the structure of the virus and the body’s natural immunity to it, and developing antibodies that fight the vaccine.

“We need to answer the really fundamental questions of understanding how the virus works, what happens when it gets into the body and why it’s different than other viruses,” said Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases.

Last year, roughly 2.5 million people contracted HIV worldwide and more than 2 million died of AIDS. More than 33 million people live with HIV.

Few scientists support putting the brakes on human trials altogether. But most experts at the meeting agreed that more caution should be used before advancing research into large-scale human trials.

The revamping shouldn’t impact total funding levels, Fauci said. The National Institutes of Health allotted $600 million for AIDS vaccine research, $500 million of that through Fauci’s agency. This adds up to about 70 percent of the money spent globally on AIDS vaccine research.

Mid-course corrections are not unprecedented in vaccine research. In the 1930s, two promising candidates for a polio vaccine failed miserably when tested on humans. One, the injection of bits of live polio virus, was ultimately blamed for six fatal cases of polio. Another, by New York University researcher Maurice Brodie, used an inactivated or “killed” virus as its base, also proved ineffective.

Scientists responded to the failures by severely scaling back the testing on humans.

In the meantime, polio cases climbed as focus shifted toward prevention strategies: perfecting the iron lung, keeping kids away from pools and frequent hand washing.

But the early failures were critical to the eventual development of a successful vaccine. When Jonas Salk began work on his polio vaccine, he pulled from Brodie’s early work, injecting the “killed,” or benign viruses into a healthy person’s bloodstream. In 1953, Salk announced that his vaccine trials were working. The vaccine was released into wide distribution four years later.

Experts are mixed as to whether history is a guide in a search for the AIDS vaccine, or whether there are insurmountable challenges.

“Vaccine research has an unpredictable time course,” said Warner Greene, co-chair of the HIV Vaccine Summit and researcher at the University of California San Francisco. “If someone says, we’ll have a vaccine by a certain date, we probably shouldn’t listen to them.”

Especially when considering the AIDS virus, which is uniquely difficult to combat.

“HIV is a hell of a more sophisticated pathogen than polio or smallpox,” Warren said.

Most vaccines work by boosting the immune system against the pathogen. But HIV attacks the immune system itself. The virus also plants itself into the body’s DNA, setting up residence in the chromosomes, and “once it integrates itself it’s almost impossible to get rid of,” Fauci said. Plus, it mutates rapidly.

“In terms of a pathogen, we’ve never encountered a pathogen with the genetic plasticity of HIV, which makes the creation of an effective vaccine difficult,” Greene said.

Scientists will continue to monitor two groups in search for clues. One group is people who are constantly exposed to HIV, but mysteriously don’t get infected. The other is those who do get infected, but are able to beat the virus down to undetectable levels. Understanding the immune responses of these individuals could provide clues to a vaccine.

“I think the idea of making a mid-course correction is all aimed at speeding the discovery of an effective vaccine,” Greene said, but then paused, adding, “But I hope it doesn’t take 42 years.”