Professors Susan Buchbinder and Larry Corey shared more details of the early closure of the Mosaico HIV vaccine clinical trial and the future of HIV vaccine research at the 30th Conference on Retroviruses and Opportunistic Infections (CROI 2023) in Seattle yesterday.
The trial, which gave the vaccine or a placebo to 3900 cis and trans gay and bisexual men and trans women in the Americas and Europe closed on 18 January after Janssen pharmaceuticals, the research branch of Johnson & Johnson reported that the study’s vaccine regimen was not effective at preventing HIV.
“The unfortunate news was that there was no efficacy seen from the results of the trial and the HIV infection rates were actually quite high,” Dr Buchbinder of the San Francisco Department of Health said during a press briefing. She reported that the overall HIV incidence was 4.1 per 100 person-years in both the vaccine and placebo arms. Incidence rates were above 5.0 in people aged 18 to 20 years in both arms, and higher in Latin America than Europe and the United States. The vaccine regimen was found to be safe with generally minor adverse reactions limited to the injection site.
Like the Imbokodo trial that ended in 2021, Mosaico tested a vaccine intended to produce non-neutralising antibodies. In contrast to neutralising antibodies that directly prevent a pathogen from spreading within the body, non-neutralising antibodies evoke immune responses that fight infection indirectly.
Corey, of the HIV Vaccine Trials Network, had previously written that the Imbokodo and Mosaico trials would be crucial in revealing whether non-neutralising antibodies could protect against HIV. However “they're not showing to be clinically effective,” Corey said. “When there's a fork in the road, take it,” he added, suggesting that moving forward their research would focus on vaccine approaches that use neutralising antibodies.
Corey said that seven or eight candidate vaccines would be evaluated within the next two years to determine whether they can achieve high enough levels of neutralising antibodies that might protect against HIV infection. “It's going to be complicated. It will take us a little time,” Corey said but also expressed hope. “The field is vibrant, and we're very optimistic.”
Buchbinder S. Overview of the Mosaico HIV vaccine trial. Conference on Retroviruses and Opportunistic Infections, Seattle, special session, 2023.
Corey L. HIV vaccine development post-Mosaico. Conference on Retroviruses and Opportunistic Infections, Seattle, special session, 2023.