The first in a series of clinical trials designed to build on the promise of an HIV vaccine that showed modest protection when tested in Thailand has passed a key hurdle, according to a new study. It paves the way for larger HIV vaccine trials to move forward in South Africa.
The trial found that the so-called Thai vaccine induced comparable immune responses when tested in South Africa as it had in the original trial. This early phase of testing was designed to see how a different population’s immune system would respond, not—yet—whether the vaccine would protect against HIV.
The results, announced Tuesday at a conference in Cape Town, are significant because participants in the Thai and South African trials varied in ethnicity, body mass index, gender and age, all of which could have affected response.
“We want to be able to develop a vaccine that can go to high-risk men and women of varying ages and weight and genetic makeup,” said Dr. Larry Corey, president and director emeritus of the Fred Hutchinson Cancer Research Center and principal investigator of the Hutch-based HIV Vaccine Trials Network, which conducted the study. “[The results of this study] tell us we should be able to do that, so that’s wonderful news.”
The 2009 Thai study was widely considered a turning point in HIV vaccine research because it marked the first time an experimental vaccine showed any protection against HIV. Participants who received the vaccine were 31 percent less likely to be infected by HIV than those who received a placebo. That was not enough protection to warrant licensing the vaccine, but it was the first evidence that developing a protective vaccine was even possible.
Dr. Anthony S. Fauci, director of the National Institute of Allergies and Infectious Diseases (NIAID), part of the U.S. National Institutes of Health, called the new findings “encouraging news as we move toward evaluating a modified and potentially improved version of the vaccine regimen in South Africa.”
NIAID, sponsored the study and funds the HVTN, the largest publicly funded global collaboration working to develop an HIV vaccine. NIAID and HVTN are part of a public-private partnership formed in 2010 specifically to follow up on the 2009 Thai vaccine study.
A second clinical trial, slated to begin in South Africa in January, will test a new version of the Thai vaccine that has been modified to both boost its potency and durability and make it potentially more responsive to the subtype of HIV that is found in South Africa, called clade C, rather than the subtype found in Thailand, or clade B. If that small trial shows that the modified vaccine is safe and again induces the anticipated immune system responses, the plan is to expand it to a larger trial in late 2016 or early 2017 that would test for efficacy, or whether the vaccine actually protects those who receive it from being infected with HIV.
“We are very excited about moving forward,” said Dr. Glenda Gray, president of the South Africa Medical Research Council and HVTN co-principal investigator and director of its Africa programs, at a media conference today in Cape Town. If all goes according to plan, results of the larger trial could be seen in two years, by 2019, Gray said.
Since 2009, scientists have been working to analyze the data of the Thai trial, gain insight into the types of antibodies and cellular immune responses induced and come up with modifications that would make the vaccine more potent and durable. Researchers also worked to develop a clade C insert for the vaccine to be tested in South Africa; as with the original Thai vaccine, the insert uses HIV pieces that are made in a laboratory and cannot cause HIV infection.
Developing a vaccine to protect against HIV has been challenging for a number of reasons. The virus kills the very immune cells used in defending the body against it. It mutates rapidly within individuals and across geographical locations, making it a moving target for vaccines. And until the 2009 Thai trial results, no vaccine candidate had shown any protection, so there were no known “correlates of protection” that scientists could search for as an early sign of whether a vaccine might be effective or use as a target for improving vaccines.
South Africa has the largest HIV epidemic in the world, with an estimated 6.1 million people infected with the virus, or almost 18 percent of the population. This means that not only is the need for a vaccine great, but that clinical trials there can be both smaller and done more quickly precisely because the population being tested is at higher risk and more likely to encounter HIV.
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. (Again 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.) Scientists and participants alike are “blinded,” or kept ignorant, of whether the injection each trial participant receives is the experimental vaccine or a placebo; the two groups are compared and statisticians tally which had more infections.
Public health experts generally want a vaccine to protect at least 70 to 80 percent of people vaccinated, but scientists and government regulators are likely to consider licensing an HIV vaccine if it protects at least 50 percent of those who receive it.
“I think we would rejoice if we had a vaccine efficacy of 50 percent,” Gray said. “We would learn so much, and could focus on improving it. Having an efficacious vaccine would be a game-changer at a global scale.”
Gray will formally present the latest study’s findings Wednesday at the HIV R4P (Research for Prevention) Conference, the first global conference to bring together all scientists working on HIV prevention science, including vaccines, microbicides and pre-exposure prophylaxis. She and other scientists stressed that a combination of measures may be required to effectively prevent HIV infection.
Mary Engel is a former staff writer at Fred Hutchinson Cancer 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.