Effectiveness has not been proven
Trials of a promising HIV vaccine have been prematurely interrupted
Ivan Shangin, Life4me+
Trials of the HIV vaccine, which experts considered one of the most promising, were discontinued ahead of schedule, writes Science. The reason for this was the extremely low results of the composition.
"There is absolutely no evidence of efficacy," said Dr. Glenda Gray, who led the vaccine research program and is president of the South African Medical Research Council (MRC) in Cape Town.
The efficacy study, which began in October 2016, covered 5,407 sexually active HIV-negative men and women aged 18 to 35 in 14 regions of South Africa. Experts randomly divided the participants 50/50 to receive doses of HIV vaccines used in one or two doses, and a placebo group. It was assumed that the observations would last until July 2022. However, on January 23, the independent monitoring commission, which analyzed the planned peak data to assess the safety and effectiveness of the composition, informed Dr. Gray and other study leaders that it "does not make sense" to continue working. 129 infections were registered in vaccinated groups and 123 in those receiving placebo.
"I was terrified," says Dr. Gray.
There is no evidence that the vaccine has caused harm, as happened in another major study on the composition of HIV, which was prematurely discontinued in 2007.
Susan Buchbinder, an epidemiologist at the University of California, San Francisco, who was one of its leaders, has already sent her condolences to colleagues in South Africa and stressed that the test was conducted at the highest level.
"The trial was incredibly well done and we got the final answer, but that's the whole point of science," says Buchbinder, who is now leading another large–scale study of the Mosaico HIV vaccine.
The discontinued study, which was funded by the MRC of South Africa, the US National Institutes of Allergy and Infectious Diseases (NIAID) and the Bill and Melinda Gates Foundation, tested a vaccine containing a recombinant version of the HIV surface protein mixed with an adjuvant (immune system booster).
Meanwhile, many scientists working in the field of HIV doubted that the study in South Africa would be successful, since the vaccines previously used in the scheme of primary stimulation of immunity showed very little when studying the effectiveness in Thailand (the study was completed in 2009). However, according to its results, the total number of cases of HIV infection in the vaccinated group was 51, and in the placebo group – 74 – the effectiveness was 31%.
Dr. Gray noted that, given the severity of the epidemic in South Africa – the country is home to 7.7 million PLHIV out of 37.9 million HIV-positive people in the world – she and her colleagues, who slightly changed the composition of the vaccine used in Thailand, felt that the new trial was worth it.
"The epidemic got out of control here, and we had to take steps to conduct a biomedical intervention," says Dr. Gray.
Meanwhile, despite the failure of the study, NIAID director Anthony Fauci said he did not regret his support:
"I don't think it was a bad choice. Because he was the only one possible."
Until today, no one knows exactly what kind of immune reactions can prevent HIV infection - the so–called correlates of immunity – but many researchers today are focused on developing a vaccine that can start the process of generating antibodies that can "neutralize" the ability of the virus to infect cells.
Fauci notes that the "Thai version" of the vaccine triggered the production of antibodies that bind to HIV, but do not neutralize it, and this is not enough.
"We have been fighting for years [to get] the slightest positive effect, a potential correlate of immunity, and it looked very promising," he says. "Given the severity of the epidemic and what we had, what would you do: something or nothing?"
Fauci notes that the Thai study involved people with a relatively low risk of infection – the frequency of new infections was about 0.3% per year – which means that the primary impulse could work if the immunity it created did not encounter repeated problems. In a study conducted in South Africa, the rate of new infections per year was about 4% among women and 1% among men.
"It's possible that the defense mechanisms were overloaded," Fauci says.
Mitchell Warren, who heads AVAC, a nonprofit community HIV prevention group, says this failure won't slow down work on vaccine development.
"There are other products in the efficacy trials," says Warren, who was on the monitoring board that recommended the South African study be discontinued.
Given the negative result of the candidate vaccine, at the moment the greatest prospects are given to the composition of Mosaico. Developed by Jannsen Vaccines, the product offers a scheme for primary stimulation of immunity by the influence of a "mosaic" of HIV genes from various virus subtypes, "stitched" by researchers into a harmless adenovirus.
In earlier trials, this vaccine also did not trigger neutralizing antibodies, but produced high levels of binding antibodies and other immune responses. The auxiliary mechanism of the vaccine consists of a mosaic version of the HIV surface protein mixed with an adjuvant.
This mixture has proven itself well in primate studies, when animals were vaccinated and then "infected" with modified VIO.
During the Mosaico trials, transgender people and men who have sex with men in North America and Europe will receive. The vaccine will also be tested in a small Imbokodo study among women in sub-Saharan Africa. The results of the latter will be presented next year, Mosaico – in 2023.
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