Photo by Robert Hood / Fred Hutch News Service
Editor's note: Fred Hutch News Service reporter Mary Engel and photographer Robert Hood are in Durban, South Africa, covering the news from the 21st International AIDS Conference.
DURBAN, South Africa — Dr. Albert Sabin, developer of the oral live virus polio, once told Dr. Anthony Fauci, “Tony, I do not think we will ever have an HIV vaccine.”
As a physician, Fauci, the long-time director of the National Institute of Allergies and Infectious Diseases, part of the U.S. National Institutes of Health, had cared for Sabin in his last days. As a friend, he had delivered the eulogy when Sabin died at age 86 in 1993.
But as a scientist, he completely disagreed with one of the preeminent figures in medical history.
“As much as I loved him, my dear friend Albert Sabin will be proven to be incorrect — one of the very, very few times that Albert ever was wrong,” Fauci told a conference hall packed with scientists on Tuesday at the biennial meeting of the International AIDS Society in Durban, South Africa.
Fauci has reason to be optimistic. As the AIDS 2016 conference got underway, the NIAID-funded HIV Vaccine Trials Network, or HVTN, based at Fred Hutchinson Cancer Research Center, was gearing up to launch a large-scale trial in South Africa in November, the first such trial to be in the field in a decade and one that could lead to the first licensed vaccine against HIV.
And within the last few months, the HVTN, working with its sister network, the HIV Prevention Trials Network, or HPTN, based in Durham, North Carolina, has begun what is already being called a landmark study to test an experimental, so-called broadly neutralizing antibody that could potentially protect people from infection by almost all strains of the rapidly mutating virus that causes AIDS.
That these two different approaches are underway at the same time is a testament to the challenge that Sabin alluded to in finding an HIV vaccine — but also to Fauci’s optimism, albeit an optimism tempered by scientific skepticism.
“The pathway to HIV vaccine,” he predicted, “will be full of surprises.”
Building on the so-called Thai vaccine
The first surprise came in 2009 when, after years of failed attempts, the first sign that an HIV vaccine was even possible came with the publication of clinical trial results of the so-called Thai vaccine, a two-vaccine regimen named after the country in which it was tested. Those who received that regimen had a 31 percent lower risk of becoming infected with HIV 3½ years after vaccination compared to placebo recipients. Although not enough protection to warrant licensing, the results were widely hailed as a breakthrough.
The protection provided by the Thai vaccine took years of study to understand.
In developing a vaccine, Fauci explained, vaccinologists typically try to mimic how the body responds to natural infections. Historically, for almost any viral infection, even the most toxic, those who survived did so because their immune systems ultimately cleared the virus — polio, smallpox, measles, mumps — and left them with immunity to that pathogen. Ever since the first vaccine — against smallpox — was developed in 1796, vaccinologists have sought to mimic that natural response.
But no one has ever cleared HIV naturally and been left with natural immunity. There was no example to mimic.
For years, no experimental vaccines provided any protection. Then came the surprising, if modest, protection achieved by the Thai vaccine, which allowed scientists for the first time to identify “correlates of protection,” or early signs of whether a vaccine might be effective. Those correlates helped establish benchmarks for a second trial, this time of a regimen altered to be more protective, longer lasting and effective against the predominant HIV subtype in South Africa, which has the largest HIV epidemic in the world.
Photo by Robert Hood / Fred Hutch News Service
In May, NIAID and the HVTN announced that a small, early-phase trial met those markers and gave the go-ahead to expand into a larger trial, conducted in South Africa, which could lead to a licensed vaccine. The goal is to reach at least 50 percent protection via a more potent, longer-lasting vaccine.
“We hope to have results in five years,” said Dr. Glenda Gray, president of the South African Medical Research Council, who as a principal investigator for the HVTN is leading the trial. “It’s going to be a very exciting five years for all of us. It’s the result of many, many, many years of hard work from basic scientists to clinicians to our trial volunteers.”
A second path
In the meantime, on a parallel track, scientists who spent years studying people with HIV had come across some who developed the broadly neutralizing antibodies that are considered the holy grail of vaccine research. The trouble is, they developed them too late to protect against infection. So scientists decided to try to work backward: find the antibodies, then try to develop a vaccine to induce them.
But first, they need to make sure the antibodies actually work against HIV. That is what the second trial is designed to find out. Skipping the vaccine step for now, it will deliver a laboratory-produced version of a broadly neutralized antibody directly via an intravenous infusion, or IV.
Robert Hood / Fred Hutch News Service
Called AMP for Antibody Mediated Prevention, the trial will be the first to test such an antibody against HIV infection in a large clinical trial. At a presentation on HIV vaccines at AIDS 2016, Dr. Nyaradzo Mgodi of the University of Zimbabwe-University of California San Francisco Collaborative Research Programme in Harare, Zimbabwe and chair of the AMP trial in Africa, called the antibody being tested “promising.”
“It has broadly neutralizing capabilities and has shown good safety results in early Phase 1 studies,” she said. “I think we will move the HIV vaccine search forward and we will have an HIV vaccine.”
Early results of the AMP study should be available by 2018, said Fred Hutch’s Dr. Larry Corey, the founder and head of the HVTN, at a press briefing Tuesday.
The AMP study in Africa will enroll 1,500 sexually active women at 15 sites in Botswana, Kenya, Malawi, Mozambique, South Africa, Tanzania and Zimbabwe. A parallel study will enroll 2,700 men and transgender people who have sex with men at 24 sites in the U.S., Brazil and Peru.
Fauci is convinced that broadly neutralizing antibodies will play an important, but not necessarily exclusive, role in a potential HIV vaccine. Corey, who is chairing the AMP study with HPTN head Dr. Myron Cohen, agrees.
“We are at a very novel place in the HIV vaccine field, where we have this strategy of neutralization and non-neutralization,” he said. “In the end, we may find that they both give partial efficacy, and we may need to combine them. But we have come a very long way.”
Read more about Fred Hutch's HIV work in South Africa here.
Mary Engel is a former staff writer at Fred Hutchinson Cancer Research Center. Previously, she covered medicine and health policy for the Los Angeles Times, where she was part of a team that won a Pulitzer Prize for Public Service. She was also a fellow at the Knight Science Journalism Program at MIT. Follow her on Twitter @Engel140.
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