8/31 J&J HIV shot fails, adding another blow to decades-long effort to curb epidemic
J&J’s HIV vaccine failed its first major trial Tuesday, handing another setback to the nearly 40-year effort to build a vaccine against one of the deadliest epidemics in history.
The candidate, which uses the same technology as J&J’s Covid-19 and Ebola shots, was among the last major HIV vaccine constructs in late-stage trials — a holdover from a wave of Big Pharma efforts that have so far gone bust.
J&J’s attempts aren’t ending, though. The latest study, a Phase II known as Imbokodo, was one of two late-stage trials testing slightly different vaccine regimens on different populations. Although Imbokodo is ending, the second study, a Phase III known as Mosaico, will continue.
“The development of a safe and effective vaccine to prevent HIV infection has proven to be a formidable scientific challenge,” NIAID director Anthony Fauci said in a statement. “Although this is certainly not the study outcome for which we had hoped, we must apply the knowledge learned from the Imbokodo trial and continue our efforts to find a vaccine that will be protective against HIV.”
With the J&J shot, researchers had been hoping to build off one of the only successes in the history of HIV vaccines. In 2009, researchers reported on a trial known as RV144 that mixed multiple different vaccine constructs together. Although the study failed, it appeared to reduce the risk of infection by 30%. It was the first sign of vaccine efficacy in the then 30-year-old epidemic.
Efforts to replicate those results, however, have so far come up flat. Last year, a Phase III trial for a vaccine developed by Sanofi and GSK showed virtually no difference between placebo and vaccine arms.
In the Imbokodo trial, volunteers received either placebo or four injections of a common cold virus (technically known as adenovirus 26) engineered to carry a “mosaic” of HIV proteins. They were also directly given a couple doses of an HIV protein called gp140 and an adjuvant meant to set the immune response in motion.
After two years, 63 of the 1,109 participants on placebo were infected with HIV, compared to the 51 of the 1,079 participants on the vaccine. Although that technically computed to 25.2% efficacy, the results were not statistically significant.
And the confidence interval for the vaccine — the range of possible efficacies that would be consistent with the trial’s results — were wide: -10.5% to 49.3%.
Although the company is ending and unblinding the Imbokodo trial, J&J said that a data safety and monitoring board decided the Mosaico trial should go on. Because the vaccine uses a slightly different regimen and studies a different patient population, it could lead to different results.
And despite the setbacks, a new generation of HIV vaccines is now entering early-stage studies. Moderna is initiating trials on an mRNA vaccine that’s meant to induce a particular type of neutralizing antibody the NIH isolated from HIV patients who show profound and unusual control over their virus. And Vir Biotechnology has started a Phase I trial on a vaccine that uses the virus CMV to teach T cells to recognize HIV proteins.
