‘Last roll of the dice’ for a near-term HIV vaccine fails

A study billed as the last chance to develop an HIV vaccine this decade has been shut down, investigators announced Wednesday at a conference in Harare, Zimbabwe.

The trial, known as PrEPVacc, was testing two different vaccine regimens on about 1,500 volunteers in East and Southern Africa. After multiple other high-profile trials failed, a PrEPVacc investigator described the study this summer as “the last roll of the dice” for an HIV vaccine until the 2030s. 

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The study has now been halted early after an independent data monitoring committee concluded there was little or no chance the study would demonstrate efficacy, researchers told the International Conference on AIDS and STIs in Africa.

Although disappointing, the news may not surprise many HIV vaccine researchers. PrEPVacc was seen as a pioneering study, both as one of the first large, African-led HIV vaccine trials and one of the first trials to incorporate PrEP, the daily antiviral pills that can dramatically reduce the risk of HIV infection. 

But the trial used older vaccine designs some scientists doubted would provide adequate protection. 

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With the failure, there are now “no HIV vaccines being trialled for efficacy anywhere in the world,” PrEPVacc investigator Pontiano Kaleebu said in a statement. 

Efforts are limited to small, early-stage trials designed to test new technologies that might stand a chance against the wiliest virus humanity has ever encountered. Kaleebu said there now had to be “greater urgency” to push these technologies forward. 

“We have come so far in our HIV prevention journey, but we must look to a new generation of vaccine approaches and technology to take us forward again,” he said. “We must also look to a new generation of leaders. We set up PrEPVacc to grow our capacity in Africa to do future trials ourselves and to develop those who will lead them here in Africa.” 

The new strategies include sending HIV “wanted” posters to a specific set of immune cells by encoding them in another, more benign chronic virus. More popular is an approach called germline targeting, where researchers give a series of different jabs designed to nudge the immune system toward making the perfect, HIV-snaring antibodies. 

Moderna, the National Institutes of Health, and IAVI (formerly known as the International AIDS Vaccine Initiative) have all invested in the latter.

“Despite these results, IAVI remains optimistic that developing an HIV vaccine is possible,” said IAVI CEO Mark Feinberg in an emailed statement. “We believe that new approaches designed to induce broadly neutralizing antibodies to HIV are the most promising path forward.” 

Trial director Eugene Ruzagira said he hopes PrEPVacc data will eventually inform new efforts. Although no new volunteers will be dosed, researchers remain blinded to who is on which regimen and will continue following participants into next year. Afterward, they’ll look at blood samples and data to try to decode precisely what went wrong.

“The option of giving up the work is off the table,” Ruzagira said. “The work needs to continue.”

Some researchers are skeptical, however, that the new technologies will ever lead to an HIV vaccine. Even as the HIV vaccine field has struggled for 40 years, companies have developed other methods of stopping transmission for extended periods: Forms of PrEP that can virtually eliminate the risk of infection with an injection every couple months. Biannual and annual injections are now in development.


Long-acting PrEP could raise the bar for how effective an HIV vaccine has to be, while also making it more difficult to run vaccine trials. Researchers, for example, may no longer be able to compare new shots to placebo.

PrEPVacc had been an early attempt to run a vaccine trial while also offering patients different forms of oral PrEP. And a portion of the study comparing two forms of oral PrEP will continue.

Longtime vaccine researchers say that even more outside-the-box trial designs may be needed for the next vaccine study, should one of the early stage projects prove promising.