An experimental HIV vaccine regimen being tested in a small clinical trial in South Africa has met the benchmarks to expand into a large-scale trial that could lead to the first licensed vaccine against the virus that causes AIDS, health officials said today.
The smaller trial, which began in February 2015 and involves 252 volunteers, is testing the vaccine regimen for safety and to see whether it elicits the predicted immune responses. It is ongoing but was designed to give researchers early feedback. The upcoming large-scale trial is scheduled to launch in November and involve 5,400 HIV-uninfected men and women in South Africa. It will test for efficacy, or whether the vaccine actually protects those who receive it from becoming infected with HIV.
Both trials are funded by the National Institute of Allergy and Infectious Diseases, or NIAID, and the Bill & Melinda Gates Foundation and conducted by the NIAID-funded HIV Vaccine Trials Network, which is headquartered at Fred Hutchinson Cancer Research Center.
“A safe and effective HIV vaccine would help bring about a durable end to the HIV/AIDS pandemic and is particularly needed in southern African, where HIV is more pervasive than anywhere else in the world,” said NIAID Director Dr. Anthony S. Fauci in a statement announcing the rollout of the large-scale trial.
Results are expected in late 2020 —39 years after the first cases of AIDS were reported and 37 years after HIV was identified as the virus that causes AIDS.
At a global health conference in San Francisco in April, Fauci described the decades-long quest to develop an HIV vaccine as “scientifically one of the most difficult challenges that we have ever faced.” HIV attacks the very immune cells used in defending the body against it and mutates rapidly within individuals and across geographical locations, making it a moving target for vaccines.
The first sign that a vaccine to protect against HIV was even possible came in 2009 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 vaccine 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 in the long struggle to develop a vaccine against the rapidly mutating virus.
And achieving even modest protection allowed scientists for the first time to identify “correlates of protection,” or early signs of whether a vaccine might be effective, which helped establish the benchmarks for the decision to expand the current trial into a large-scale licensure trial.
For the South Africa studies, the Thai vaccine regimen was altered with the aim of making it more protective as well as longer-lasting. (The original regimen appeared to have been 60 percent effective one year after vaccination, but protection waned.) It was also modified to be specific to HIV subtype C, the predominant HIV subtype in southern Africa. As with the original Thai regimen, the clade C insert uses HIV pieces that were made in a laboratory and cannot cause HIV infection.
A partnership of research groups, drug developers, and funders called the P5 (for Pox-Protein Public-Private Partnership) was formed in 2010 to follow up on the results of RV144, as the Thai trial was named. It has focused on South Africa, which has the largest HIV epidemic in the world, with an estimated 6.3 million people infected with the virus, or about 19 percent of the adult population.
Because it is unethical to deliberately expose people to HIV, testing to see whether a vaccine provides protection involves waiting several years and seeing how many people become infected naturally. Also for ethical reasons, all participants are counseled on HIV prevention and offered options such as condoms and male circumcision to reduce the risks of contracting the virus. All participants will receive a total of five injections over a year, with volunteers randomly assigned to either the experimental vaccine or a placebo.
The larger trial, called HVTN 702, will be led by Dr. Glenda Gray, president and chief executive officer of the South African Medical Research Council (which is part of the P5 partnership), a research professor of pediatrics at the University of the Witwatersrand, a director of the Perinatal HIV Research Unit at Chris Hani Baragwanath Hospital in Soweto, South Africa and a principal investigator of the HVTN. A lifelong South African, her drive to fight HIV was forged in the fight against apartheid.
"We have a huge burden of HIV in South Africa," Gray said today at an HVTN meeting in Washington D.C. "We are struggling to roll out treatment. The only sustainable way to impact the epidemic in South Africa is to find an efficacious vaccine. This is the fruit of almost a decade of collaboration with the P5 group to realize a vaccine. We need an AIDS-free generation. We need a future without AIDS."
Even as it plans the rollout of HVTN 702 later this year, the HVTN — the largest global network striving to develop vaccines to prevent HIV —has begun investigating a second path to an HIV vaccine. Partnering with a sister network, the HIV Prevention Trials Network, it launched a clinical trial last month on an approach called antibody mediated prevention, or AMP. Two parallel AMP clinical trials will eventually involve more than 4,000 participants in the United States, South America, and southern Africa.
Rather than delivering a vaccine, the AMP trial will use an intravenous infusion, or IV, to deliver so-called broadly neutralizing antibodies (or a placebo) to trial participants. Such antibodies are considered the “holy grail” of HIV vaccine researchers because they could potentially protect people from infection by almost all strains of the virus. But so far, no one has figured out how to make a vaccine that induces them. (The experimental vaccine regimen tested in Thailand and the modified version being tested in South Africa elicit antibodies, but they are not broadly neutralizing.)
If the experimental antibodies being tested in the AMP trial provide protection as hoped, information gleaned from the study could help scientists figure out how to reverse-engineer a vaccine to elicit the antibodies at the concentrations needed.
Fred Hutch’s Dr. Larry Corey, HVTN founder and director, believes that the path to the promised land of a vaccine that is 80 percent to 90 percent effective may well end up combining both approaches.
“HIV, one of the trickiest diseases on the planet, has been a difficult adversary. But a renaissance is taking place in our understanding of the virus,” he and Nobel laureate Dr. David Baltimore wrote in an op-ed published in Forbes on Tuesday. “Potential vaccine precursors have emerged that provide optimism that our sustained scientific efforts are paying off.”
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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.