In what has become an all too familiar—and depressing—outcome in the decadeslong search for an effective AIDS vaccine, yet another candidate has failed in a large-scale study.
A vaccine made by Johnson & Johnson (J&J) offered no convincing protection against HIV infection in the trial, dubbed Imbokodo, which began in 2017 and involved 2600 women in South Africa and four neighboring countries. “We have to fundamentally relook at what we’re doing,” says Glenda Gray, who heads the South African Medical Research Council and oversaw the protocol for the trial, which compared the efficacy of the vaccine to a placebo.
The results, announced today by J&J in a press release, found 63 infections in the placebo group versus 51 in participants who received the vaccine, for an efficacy of 25.2%–too low to make the vaccine useful. (There also was a wide “confidence interval” in that result, and it did not reach statistical significance.) No safety concerns surfaced in the trial, which received support from both the U.S. National Institute of Allergy and Infectious Disease (NIAID) and the Bill & Melinda Gates Foundation.
Gray stresses that Imbokodo produced more-promising data than two other disappointing AIDS vaccine efficacy trials she helped run. “Each failed trial tells us something,” she says. Unlike the others, the study revealed glimmers of efficacy, which could reveal protective immune responses and allow researchers to “design a better vaccine for the future.”
J&J’s chief scientific officer, Paul Stoffels, says despite the failure, a second efficacy trial of a similar vaccine in a different study population will continue. That Mosaico trial, which is taking place in the Americas and Europe and started in 2019, involves 3800 men who have sex with men and transgender people. Stoffels notes that Mosaico is fully enrolled and is evaluating the ability of an improved version of the vaccine to protect against transmission through the rectal, rather than the vaginal, route. An HIV vaccine, Stoffels says “is a high hurdle, and [these results are] disappointing but also we don’t give up.”
Both Imbokodo and Mosaico combine a total of four doses of two different shots. The first uses the same backbone as J&J’s COVID-19 product: adenovirus 26, a harmless ”vector” that, in this case, shuttles four HIV genes into human cells. The different HIV genes were engineered to produce HIV proteins that provoke an immune response broad enough to protect against a wide range of virus strains. The second shot consists of a genetically engineered version of HIV’s surface protein, although the exact protein differs between the two studies.
NIAID’s HIV Vaccine Trials Network is sponsoring both studies. Lawrence Corey, a vaccine researcher at the Fred Hutchinson Cancer Research Center who co-leads this network, notes that the J&J strategy relied heavily on triggering the production of T cells that could identify and clear HIV-infected cells. Other groups have taken a different approach, banking on producing high-quality “neutralizing” antibodies that can prevent the virus from even infecting cells. Corey says if the T cell strategy fails to gain traction in the near future, “it really does mean the entire field needs to shift to neutralizing antibodies.”
Several research groups have begun human trials of vaccines designed to spur potent neutralizing antibodies against HIV, but none will likely enter full-scale efficacy trials for about 4 years, Corey says. “We have our work cut out for us,” he adds. “Maybe COVID vaccines will give us a lesson about how to speed this up.”