HMS/MGH’s Bruce Walker presents update on vaccine progress

Bruce Walker recalls sitting across from a person long-infected with HIV who never took antiretroviral drugs and never developed AIDS. Walker remembers thinking that the person’s body held a secret of which even they were unaware: how to stop the global AIDS pandemic.

“You just feel like the answer is within these people,” Walker said. “Our mission is to take that bedside observation and go back to the lab and figure out what’s going on.”

Walker, a professor of medicine at Harvard Medical School and Massachusetts General Hospital and head of the Partners AIDS Research Center, is working today to uncover that secret in a large international study of 2,000 people whose bodies control the HIV virus without the assistance of drugs or other treatments.

“I think we have real reason to be optimistic because one in 300 people who are infected are [controlling the virus] on their own,” Walker said.

Walker discussed his ongoing research at the Science Center Friday (Sept. 19) as well as the professional journey that led him to the front lines of the AIDS pandemic — South Africa’s Kwa-Zulu Natal Province. Walker has played a large role in the establishment of a state-of-the-art lab at the Nelson Mandela School of Medicine at the University of Kwa-Zulu Natal in Durban.

Walker was speaking as part of the Program for Evolutionary Dynamics’ Distinguished Lecture Series, designed to provide scientific leaders with the opportunity to address a general scientific audience.

In his comments, Walker gave an overview of HIV and AIDS and of progress in making a vaccine. Though the existence of HIV “controllers” is cause for long-term optimism, Walker said the immediate prospects for a vaccine are dim.

The 2007 failure of the Merck vaccine, which may have actually increased subjects’ risk of contracting HIV, sent shock waves throughout the HIV vaccine community, effectively shutting down efforts that attacked the virus in similar ways.

“What happened was the worst possible outcome that anyone could have imagined,” Walker said. “It’s really brought the field to a crashing halt.”

Walker said Friday that he believed a vaccine is at least a decade away from use in poor settings around the world.

And a vaccine is badly needed. Walker first went to South Africa in search of samples to use in laboratory studies of HIV. He came away with a firsthand view of the destruction the virus is wreaking in the poorest parts of the world and with a realization he had to do more. From that first exposure, he and colleagues began to establish clinical programs at nearby hospitals not only to study the virus but also to treat those afflicted with it. He went on to found the lab at the Mandela School of Medicine to provide research capacity close to the location where clinical care is being given.

“When I went over there, I was completely shell-shocked by what I saw,” Walker said.

In most people infected with HIV, the virus is always a step ahead of the immune system, mutating so quickly the immune system can’t keep up. Those who control HIV on their own seem to fall into two categories, Walker said: “elite controllers,” whose bodies are so efficient that there is no sign of the virus, and “viremic controllers,” whose bodies keep the virus at a low enough level that it can’t cause disease.

Though participants are still being enrolled in the study, Walker said it appears the controllers’ bodies slam the virus with an overwhelming immune response right away. HIV’s ability to mutate, which makes it so hard to treat, allows it to survive that initial attack, but the virus is forced to mutate into a benign form. That change affects its ability to replicate and makes it less able to cause disease.

Other studies of the virus’s response to drugs shows that it tends to mutate in predictable ways in response to different attacks. If researchers studying the controllers can figure out how to force the virus to mutate in ways that weaken the virus, a vaccine might be possible, Walker said.

“We think there are constraints on HIV evolution,” Walker said. “If we can keep it boxed in and make it take a path it really doesn’t want to, we may have a chance.”