The only HIV vaccine in a late-stage trial fails

[reader]

Benjamin Ryan and Matt Lavietes

The only HIV vaccine in a late-stage trial has failed, researchers announced Wednesday, dealing a significant blow to the effort to control the global HIV epidemic and adding to a decadeslong roster of failed attempts.

Known as Mosaico, the trial was the product of a public-private partnership including the U.S. government and the pharmaceutical giant Janssen. It was run out of eight nations in Europe and the Americas, including the U.S., starting in 2019. Researchers enrolled nearly 3,900 men who have sex with men and transgender people, all deemed at substantial risk of HIV.

The leaders of the study decided to discontinue the mammoth research effort after an independent data and safety monitoring board reviewed the trial’s findings and saw no evidence the vaccine lowered participants’ rate of HIV acquisition.

“It’s obviously disappointing,” Dr. Anthony Fauci, who as the long-time head of the National Institute of Allergy and Infectious Diseases (NIAID) was an integral partner in the trial, said of the vaccine’s failure. However, he said, “there are a lot of other approaches” early in the HIV-vaccine research pipeline that he finds promising.

“I don’t think that people should give up on the field of the HIV vaccine,” Fauci said.

Fauci said that a critical limitation of the Mosaico vaccine was that it elicited what are known as non-neutralizing — as opposed to neutralizing — antibodies against HIV.

“It is becoming clear,” he said, “that vaccines that do not induce neutralizing antibodies are not effective against HIV.”

Up-and-coming HIV vaccine innovations, including efforts that rely upon the cutting-edge mRNA vaccine technology behind some of the coronavirus vaccines, may hold the key, Fauci said.

The critical problem that has bedeviled HIV vaccine research for decades, Fauci noted, is a crucial weakness that the virus already successfully exploits: The natural immune response to infection is not sufficient to thwart the virus.

In the decades since, there have been nine late-stage clinical trials of HIV vaccines, including Mosaico and Imbokodo, plus one, called PrEPVacc, that is still underway in Africa. However, the vaccine in PrEPVacc is not considered to be on a direct path to licensure if it demonstrates efficacy. Only one of these vaccines has shown any efficacy — and only at a modest level, not considered robust enough for regulatory approval — in a trial conducted in Thailand between 2003 and 2006, the findings of which were published in 2009.

In the years since, a phalanx of global researchers has studied the Thai trial in hopes of developing insights to inform further HIV-vaccine development.

The yearslong effort to design the Imbokodo and Mosaico vaccines was in part grounded in an attempt to build on the modest success of the Thai trialin hopes of developing insights to inform further HIV-vaccine development.

“We had hoped that we would see some signal of efficacy from this vaccine,” said Dr. Susan Buchbinder, an epidemiologist at the University of California, San Francisco, who co-led the Mosaico trial. She added that, promisingly, as in the Imbokodo trial, there were no evident concerns about the vaccine’s safety.

Jennifer Kates, director of global health and HIV policy at Kaiser Family Foundation, said the trial’s failure is a “stark reminder of just how elusive an HIV vaccine really is and why this kind of research continues to be important.”

“Fortunately, there are a number of highly effective HIV prevention interventions already,” Kates added. “The challenge is to scale them up to reach all at risk.”

Pre-exposure prophylaxis, or PrEP, in which people at risk of HIV take antiretroviral medications in advance of potential exposure to the virus, is highly effective at preventing infection but remains vastly underutilized in the U.S. and around the world.

Additionally, research published in the mid-2000s showed that voluntary medical male circumcision lowers the risk of female-to-male HIV acquisition by about 60%. This led to a major effort to promote circumcision in sub-Saharan Africa, home to two-thirds of the HIV cases in the world.

Globally, an estimated 38.4 million people were living with HIV in 2021, according to the Joint United Nations Programme on HIV/AIDS. Some 1.5 million people currently contract the virus annually, a figure that has more than halved since its peak in 1996.

[vinapu]

one day somebody will find something as for sure scientists will find issue challenging until  solved

[bkkmfj2648]

I personally know how frustrating these vaccine trials can be.

After a high % of my friends died from AIDS during the 1980s, I agreed to be a volunteer for the VaxGen 3 year trial period, which if I remember correctly ran from 1998 - 2000.

It was also unsuccessful - as it was deemed to be only 17% effective.

It was my small way to do something for the loss of life of so many of my friends.