Featuring Our Faculty: Search for HIV’s Holy Grail: New Plan of Attack in SF

Scientists have had profound success in treating and preventing HIV and AIDS, turning what was once an almost-certain death sentence into a condition now labeled a chronic illness. But the Holy Grail has remained elusive.

A vaccine could end the global AIDS epidemic just as vaccines have wiped out smallpox, and nearly done the same for polio. But finding one that prevents HIV infection has proved immensely frustrating and disappointing.

A team of U.S. scientists have a new plan of attack, though, and clinical trials have started in San Francisco and a dozen or so other sites around the country. The therapy being tested isn’t quite a vaccine — it’s a bit of a cheat, in a way — but if it works, it could be the first step in finally conquering the greatest remaining challenge in HIV science.

“What we’re testing isn’t what we would assume would be the final product. But this will give us a benchmark,” said Dr. Susan Buchbinder, who is running the San Francisco arm of the trial through the Department of Public Health. “The goal here is to prove this approach will work.”

The approach is what’s known as passive immunity. Vaccines generally work by injecting people with a virus in a safe, controlled way to trigger an immune reaction, which includes corralling antibodies to fight the specific virus. Then when people are exposed to the same virus later, their bodies will be able to quickly mount an aggressive defense and ward off infection.

In passive immunity, scientists would skip a step. Instead of giving people a small sample of the virus so they can create their own antibodies, doctors would inject people with the antibodies themselves.

In the new HIV trial — called the AMP study, for antibody mediated prevention — participants get an intravenous infusion of an antibody that is known to attack the virus and stop it from reproducing and causing illness. Only a small percentage of people produce this antibody naturally when they’re exposed to HIV.

If the infusion proves effective in the trial, the next step would be finding a way to get the body to produce those antibodies on its own, as in traditional vaccines. Otherwise, people would need to get regular infusions — perhaps every four to eight weeks — to keep their antibody levels up.

Eternal protection is goal

“To be able to immunize someone and walk away and confidently know they are protected forever, that’s very different from saying you need to come back in two months to get another injection. That’s why vaccination is the Holy Grail,” said Dr. Warner Greene, director of the Gladstone Institute of Virology and Immunology, who has studied HIV vaccines but is not involved in the new research.

Making an HIV vaccine has proved challenging largely because the virus is a bit of a chameleon. It’s constantly mutating, which allows it to evade the normal immune response that the body uses to battle infections. The body, over time, can eventually fight off the vast majority of viruses, from those causing the common cold to more serious ones such as pneumonia and even Ebola.

But that’s not the case with HIV. So once infected, almost everyone needs to take antiretroviral drugs for the rest of their life to keep the virus under control. Those drugs are lifesaving, but they don’t kill all the virus and aren’t a cure.

Previous vaccine research has failed when the body, even when given an immunity booster, couldn’t keep up with the ever-changing virus. Antibodies that seemed to work at first would stop working when the virus mutated and became resistant to them.

Thread of hope

The new trial is testing what’s known as a “broadly neutralizing” antibody. The antibody, called VRC01, targets a specific site on the outer shell of HIV that doesn’t mutate and is found on almost all strains of the virus. Scientists discovered the antibody more than a decade ago, but it’s only in the past five or six years that they’ve been able to isolate it and reproduce it in a lab, allowing them to manufacture it for injection.

The work is drawing some cautious optimism from vaccine researchers who have weathered decades of disappointment. The antibody still faces years of testing — results from the current trial may not be available until 2022 — but already it’s offered a thread of hope.

“This is a very important experiment. It will tell us whether or not having these antibodies in a person actually does prevent disease,” said Stanford biochemist Peter Kim.

Kim is well familiar with the dismal history of HIV vaccine research. About 15 years ago, he led trials at pharmaceutical giant Merck on an especially promising vaccine — “the best hope we had,” Kim recalled — that ultimately failed. “It was a very depressing moment for the AIDS/HIV vaccine community,” he said.

In the intervening years, vaccine scientists have been trying to regroup. So it’s nice to see some enthusiasm again, Kim said. He has his own new research, too, studying a different antibody that also attacks a piece of the virus that isn’t prone to mutation.

Vaccines aren’t close

“It’s fair to say that the vaccine field is still back at square one,” Kim said. “But there are some promising approaches being taken that will hopefully move us forward.”

At Bridge HIV, the clinic run by the San Francisco Department of Public Health where the AMP study is taking place, researchers have been impressed by the excitement in their participants. For this trial, they’re enrolling only men who have sex with men and transgender people, but they’re already getting more interest than they can keep up with, Buchbinder said.

Ultimately, 2,700 people will join the trial in the United States, Brazil and Peru. Later, 1,500 women will be studied in parts of Africa.

It’s not an especially easy trial — for two years, volunteers have to come in every other month for 45-minute intravenous infusions. Two-thirds of participants get the antibody, and the rest get a placebo. Neither patients nor doctors know who’s getting which treatment. The trial is testing both for safety of the infusion and whether it’s effective.

Brandon Kazen-Maddox, 27, said the inconvenience is worth the potential benefits. Personally, he hopes he’s getting the antibodies and with them, some measure of protection — though doctors are quick to tell him that he can’t count on that.

“It’s a little bit of sacrificing your own body for the sake of science,” Kazen-Maddox said as he sat on an exam table while a doctor prepared to insert an IV needle for the infusion. “I know that our world needs as much protection and health options as possible. And the only way we can get these things is through studies like this.

“No matter the outcome,” he said, “at least I did something.”

Erin Allday is a San Francisco Chronicle staff writer. Email: [email protected]

About the study

The San Francisco Department of Public Health is still enrolling people in the trial. Participants must be transgender people or men who have sex with men. They must be HIV-negative. For more information, go to www.PowerToPreventHiv.org, email [email protected] or call (415) 437-7485. An informational meeting will take place June 29 at 6 p.m. at Pro Arts Gallery in Oakland.