Johnson & Johnson’s HIV vaccine fails first efficacy trial

An HIV vaccine using the same basic technology as Johnson & Johnson’s Covid shot failed to prevent infection, the company said Tuesday, dealing yet another blow to efforts to create a vaccine against the virus.

The study, called Imbokodo, enrolled 2,600 women in southern Africa who were at very high risk of HIV infection. J&J and its partners, including the National Institutes of Health and the Bill & Melinda Gates Foundation, launched the study in 2017 and announced that all participants had received either a vaccine or a placebo last year. The goal of the vaccine was not to completely prevent infection, but to reduce the chance of infection by half.

“If a vaccine is 50% efficacious 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 said that the actual efficacy seen was 25.2%, meaning those that received the vaccine had their odds of becoming infected reduced that much compared to the placebo group 24 months after the first dose. That difference was not statistically significant, indicating that it is possible the result is due to chance.

A second study, called Mosaico, that is testing a somewhat different vaccine regimen in men who have sex with men and transgender people in the Americas and Europe, will continue.

“The development of a safe and effective vaccine to prevent HIV infection has proven to be a formidable scientific challenge,” Anthony Fauci, the director of the National Institute of Allergy and Infectious Diseases, 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.”

Scientists have been trying for decades to develop an HIV vaccine. After a Merck vaccine failed to prove effective in 2007, researchers looked back at the data and found it raised the risk of people developing the disease. Hopes were buoyed by a 2009 study in Thailand, which showed limited but significant efficacy, reducing the rate of infection by about 30%. But last year, an effort combining vaccines from Sanofi and GlaxoSmithKline also failed to prove effective.

J&J had repeatedly expressed optimism about its vaccine. In 2015, Johan Van Hoof, who leads J&J’s vaccine R&D, pointed to data showing that, in animals, the vaccine could reduce infection by 90%, “suggesting it might be a real breakthrough with regard to a future HIV vaccine.” On calls with financial analysts in 2020 and 2021, Stoffels listed the HIV project among the company’s vaccine efforts, 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 means “rock” in isiZulu, and refers to a proverb about women’s strength and the need for community.

In the study, 63 of 1,109 volunteers in the placebo group developed HIV, while 51 of the 1,079 volunteers who received the vaccine developed HIV. That difference leaves a great deal of uncertainty as to whether there was an effect. The 95% confidence interval, used by researchers to define a range of likely outcomes, ranged from -10.5% to 49.3%.

However, J&J said in its release that no vaccine-related safety issues were identified. Stoffels told STAT that it was clear the vaccine did not increase the risk of HIV. 

Larry Corey, the principal investigator of the HIV Vaccine Trials Network, which helped run the study, and a professor at the Fred Hutchinson Cancer Research Center in Seattle, said that he saw the result as a disappointment but also a sign of progress. It had been hoped that non-neutralizing antibodies – those that bound to the virus but did not entirely stop infectivity – would be enough to slow the rate of HIV infection, he said, but it is beginning to appear that vaccine developers will need to figure out how to generate antibodies that neutralize the virus.

“It is telling us that non-neutralizing antibodies are not decreasing acquisition and maybe demonstrates how difficult and different HIV is than Covid-19,” Corey said.

Like the Covid-19 vaccine that Johnson & Johnson developed, this HIV vaccine delivers genetic code for proteins to a recipient’s cells using a type of virus called an adenovirus, which then makes proteins that the immune system learns to recognize and attack. The strain of adenovirus used, called Ad26, is also used in Johnson & Johnson’s experimental vaccine against respiratory syncytial virus, which can be very serious in infants.

The HIV vaccine regimen tested repeated dosing. It was given four times, and included genetic code for a “mosaic” of proteins from different strains of the HIV virus. Patients also received soluble protein injections at the third and fourth visit.

The ongoing Mosaico study – the one in the Americas and Europe – uses a different mixture of soluble proteins at the vaccination visits three and four. Stoffels said that this is one reason that the vaccine might perform better in that study. Another is that the volunteers in the Mosaico study are at lower risk of infection, which may make the vaccine’s work less difficult.

Corey also said there was hope Mosaico would succeed where Imbokodo failed. He said that the new formulation had led, in earlier studies, to higher levels of antibodies against HIV.

Stoffels said that he doesn’t believe that the result should color people’s feelings about J&J’s adenovirus vaccine platform, which, he pointed out, has proven effective against Covid-19 and Ebola. (In Covid-19, the broad use of the vaccine also was linked to a rare but severe side effect that involves both the formation of clots and excessive bleeding. That side effect is so rare even large clinical trials might not detect it.)

“It shows again that the HIV virus is a very special virus, very unique, escaping the immune system and finding its way to infect people and it’s very difficult to mount immunity against acquisition of HIV,” Stoffels said.

But researchers will continue to try. Moderna recently began human trials of an HIV vaccine that relies on the mRNA technology behind its Covid vaccines.

Corey pointed out that even under Covid lockdowns, women in the study still had a 4% chance of contracting HIV. That underscores the need for a vaccine, he said.

“Vaccines really do make a difference when you have an effective vaccine, look at what happened with Covid,” Corey said. “I think we can’t give up.”