AIDS 2016: How Seattle scientists’ frustration turns to hope in hunt for an HIV vaccine

Margaret Mazyambe works inside Cape Town HVTN Immunology Laboratory in Cape Town, South Africa. The 10,000-square foot laboratory, designed similarly to Fred Hutchinson’s Seattle headquarters, serves as a hub for the HIV Vaccine Trials in South Africa. (Credit: Erika Schultz/The Seattle Times)

Editors note: As part of our coverage of the 21st International AIDS Conference, we are reposting part two of a series from the Seattle Times about the Fred Hutchinson Cancer Research Center’s effort to find an effective HIV vaccine. View the full report here.

CAPE TOWN, South Africa — It was the question on everybody’s mind. “I know there’s a rumor that the vaccine can infect us. What do you say about that?”

The young man was at a May event in Soweto publicizing two new HIV-prevention studies, including one testing a vaccine. Both are being conducted by an international network headquartered at the Fred Hutchinson Cancer Research Center.

Busi Buthelezi, the emcee, jumped in. As long as she and other community advisers to the studies are standing, she said, “It will never happen … Never.”

No one, of course, talked about the network’s last big HIV-vaccine study.

The devastating news came in 2007. Participants in a highly promising clinical trial who got that experimental vaccine were getting HIV at a higher rate than those receiving the placebo. The HIV Vaccine Trials Network (HVTN) study was taking place in North and South America and Australia, while a parallel trial was starting in South Africa.

Scientists stopped the studies, but they didn’t know what had gone wrong. They still don’t.

In South Africa, “There was a big backlash,” said Dr. Wolfgang Preiser, professor of medical virology at Cape Town’s Stellenbosch University. He recalled the country’s health minister at the time saying it was “unacceptable” for scientists to come to South Africa and put participants at risk.

Even so, “I think the investigators were far more blown away than the participants,” said Dr. Linda-Gail Bekker, one of the leading South African scientists involved in the network’s research. “You warned us,” she said the participants acknowledged, referring to the unpredictability of science.

Researchers’ sense that they could cause harm “changed how we do business,” said Bekker, who is deputy director of Cape Town’s Desmond Tutu HIV Centre. This time, independent monitors will check results more frequently and call things off sooner, if necessary.

Meeting at a bakery in a verdant Cape Town suburb, encompassing a rugby field and gracious, walled-in homes, Bekker was upbeat. The night before, she was on a conference call with key figures in the upcoming vaccine trial, including Seattle-based HVTN scientists Dr. Larry Corey and Dr. Julie McElrath. Everyone agreed: Preliminary results from a small, ongoing safety trial of the vaccine were uniformly positive. The big trial planned for November was on.

“It’s a wonderful story,” Bekker said.

And a surprising one.

Frustration, then promise

In the early 2000s, a research division of the U.S. military and the Thai government embarked on an HIV-vaccine study in Thailand. Expectations were low.

“Since the late ’80s, trying for a vaccine has been a frustrating scientific endeavor,” said Corey, who helped develop the breakthrough HIV drug AZT. He went on to become president of Fred Hutch and returned to AIDS research as an HVTN principal investigator in 2014.

Results from the Thai trial, announced in 2009, were more positive than anything that had come before: 31 percent efficacy.

“We spent a lot of time trying to figure out why,” said Corey.

What Fred Hutchinson’s McElrath and colleagues around the world subsequently discovered is that previous test vaccines had done “exactly what not to do,” Corey said. Those vaccines had eliminated a part of the virus that helped stimulate the immune system.

Still, the Thai results were mediocre; the goal is at least 50 percent effectiveness. So researchers went back to the lab to create a better vaccine, one suited for the place where it is needed most – southern Africa, which has a different HIV subtype than Thailand.

The trial soon to start in South Africa will add a shot, making for five injections instead of four over the course of a year, and will incorporate a new substance meant to boost the immune response.

All the while, scientists, including at Fred Hutch, have separately been studying people who have what are known as “broadly neutralizing antibodies.” These people are infected with HIV, yet the disease does not progress. Corey calls their antibodies, which resist various subtypes of HIV, the “holy grail” of the HIV vaccine quest.

In the last five or six years, he said, scientists developed technologies to fish out these antibodies. The National Institute of Allergy and Infectious Diseases did so with one antibody, which has since been copied numerous times to make an infusion given through an IV drip to participants of two trials in Africa and the Americas.

Corey concedes the 30- to 60-minute procedure, given every couple of months in the antibody mediated prevention studies, is impractical. And that’s why no product is expected any time soon.

But if the trials show the procedure works, he said, maybe scientists could develop an infusion that lasts for six months, or 12, or even years at a time.

Better yet, he said, maybe they could work backward and design a vaccine to stimulate these antibodies.

Dr. Francois Venter, deputy executive director of Wits Reproductive Health & HIV Institute, is not holding his breath. Although his Johannesburg institute is one site for the antibody study, he stressed that vaccine development takes time. Mathematical modeling shows “The point from finding it works to seeing it having a public-health impact is 15 years,” he said. “The 15-year push button hasn’t even started yet.”

That, and a string of failed trials over 16 years, is why Stellenbosch’s Preiser said the vaccine field “is not very sexy at the moment.”

Aware of the skepticism, HVTN has kept publicity about the trials relatively low-key, although the network plans to discuss them at the 21st International AIDS Conference in Durban, which began Monday.

“We do operate under the radar,” said Dr. Glenda Gray, a principal investigator with the network as well as president of the South African Medical Research Council. Yet Gray could not resist some optimism.“ At the end of five years, we will have so much information.”

Read more at the Seattle Times

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