Johnson & Johnson said Tuesday that an HIV vaccine based on the same fundamental technology as its Covid injection failed to prevent infection, delivering another setback to attempts to develop a vaccine against the virus.
The Imbokodo trial recruited 2,600 women in southern Africa who were at very high risk of contracting HIV. J&J and its collaborators, including the National Institutes of Health and the Bill & Melinda Gates Foundation, began the research in 2017 and reported last year that all participants had received either the vaccination or a placebo. The vaccine's objective was not to entirely avoid infection but to significantly decrease the likelihood of disease by half.
"If a vaccine is 50% effective, it can curb the future of the HIV pandemic," said Paul Stoffels, J&J's chief scientific officer and, before that, an HIV researcher. He noted that the actual effectiveness seen was 25.2 percent, which means that individuals who got the vaccination had their risk of infection lowered by that much when compared to those who received a placebo 24 months after the first dose. That difference was not statistically significant, indicating that the finding might be coincidental.
A second trial, Mosaico, will continue to evaluate a slightly modified vaccination regimen among males who have had sex with men and transgender individuals in the Americas and Europe.
"The development of a safe and effective vaccine to prevent HIV infection has proven to be a formidable scientific challenge," Anthony Fauci, the National Institute of Allergy and Infectious Diseases director, 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."
For decades, scientists have been attempting to create an HIV vaccine. After a Merck vaccine failed to demonstrate effectiveness in 2007, researchers examined the data. They discovered that it increased the chance of getting the disease. Hopes were bolstered by a 2009 trial in Thailand, which shown modest but substantial effectiveness, decreasing infection rates by about 30%. However, an attempt last year to combine vaccinations from Sanofi and GlaxoSmithKline also failed to demonstrate the efficacy.
J&J has always expressed confidence in its vaccine. In 2015, Johan Van Hoof, who heads J&J's vaccine research and development, cited evidence indicating that the vaccine may decrease infection by 90% in animals, "suggesting it could be a true breakthrough in terms of a future HIV vaccine." In 2020 and 2021, during meetings with financial analysts, Stoffels mentioned the HIV study as one of the company's vaccination initiatives, calling it "very encouraging."
When the trial began five years ago, Fauci had said, "the development and delivery of a preventive HIV vaccine that is safe and at least moderately effective would help bring about a durable end to the HIV/AIDS pandemic."
Imbokodo, which translates as "rock" in isiZulu, is a proverb emphasizing women's strength and the importance of community.
The 95 percent confidence interval, which researchers use to establish a range of possible outcomes, varied between -10.5 percent and 49.3 percent. 63 of 1,109 placebo-treated participants developed HIV in the research, whereas 51 of 1,079 vaccine-treated volunteers developed HIV. This discrepancy raises significant doubts about the possibility of an impact.
J&J said in their statement, however, that no vaccine-related safety concerns were found. According to Stoffels, it was evident that the vaccination did not raise the chance of contracting HIV.
Larry Corey, the lead investigator of the HIV Trials Network and a professor at Seattle's Fred Hutchinson Cancer Research Center, described the finding as disappointing and a sign of progress. It was hoped that non-neutralizing antibodies – those that bound to the virus but did not wholly inhibit its infectivity – would be sufficient to slow the rate of HIV infection. Still, it is becoming clear that vaccine developers will need to figure out how to generate antibodies that neutralize the virus.
"It shows that non-neutralizing antibodies do not reduce acquisition and maybe illustrates how tough and distinct HIV is compared to Covid-19," Corey said.
As with Johnson & Johnson's Covid-19 vaccine, this HIV vaccine provides the genetic code for proteins to the recipient's cells through an adenovirus, which subsequently produces proteins that the immune system learns to identify and attack. The adenovirus strain employed is called Ad26. It is also utilized in Johnson & Johnson's experimental vaccination against the respiratory syncytial virus, which may be fatal in babies.
Repeated dosage was evaluated in the HIV vaccination regimen. It was administered four times and included genetic coding for a "mosaic" of proteins from several HIV strains. At the third and fourth visits, patients also got soluble protein injections.
At vaccination visits three and four of the ongoing Mosaico trial – in the Americas and Europe – a new combination of soluble proteins is used. According to Stoffels, this is one reason why the vaccination may have performed better in that trial. Another advantage of the Mosaico trial is that the volunteers are at a reduced risk of infection, making the vaccine's job easier.
Additionally, Corey expressed optimism that Mosaico would flourish where Imbokodo failed. He said that the new formulation had resulted in increased levels of anti-HIV antibodies in previous trials.
Stoffels said that he does not think the outcome should influence public perceptions of J&J's adenovirus vaccine platform, which he noted had effectiveness against Covid-19 and Ebola. (In Covid-19, widespread use of the vaccine was also associated with a rare but serious adverse event, including clot formation and extensive bleeding. That negative impact is so uncommon that even comprehensive clinical studies may miss it.)
"It shows again that HIV is a very special virus, very unique, escaping the immune system and finding its way to infect people, and it's challenging to mount immunity against the acquisition of HIV," Stoffels said.
However, researchers will continue to make attempts. Moderna has initiated human trials for an HIV vaccine using the same mRNA technology as its Covid vaccines.
Corey noted that even with Covid lockdowns, the study's women had a 4% risk of acquiring HIV. This highlights the critical need for vaccination, he added.
"Vaccines do make a difference when they are successful; consider what occurred with Covid," Corey said. "I think we cannot give up."