Will We Ever Have a Vaccine for HIV?

What’s more, the HIV virus has a different structure that sets it apart from other common viruses, Wessner notes. “The surface proteins on it are heavily coated with sugars,” he says. “This makes it harder for our immune system to recognize the virus’ proteins and mount a response.”

There’s one more hurdle that makes the development of an HIV vaccine challenging: When you’re exposed to a virus, either through infection or a vaccine, your body develops antibodies, or proteins that your immune system makes to help fight the virus. These antibodies also protect you against future infection. But most people infected with HIV don’t develop what’s known as broadly neutralizing antibodies, which are needed to fight variants, as they do with other viruses, Wessner explains. That means their bodies can’t clear the virus after an initial infection, and it also makes it much harder for potential vaccines to block new infections.

How the COVID-19 pandemic helped — and hindered — HIV vaccine development

The mRNA vaccines approved to prevent infection with COVID-19 were revolutionary. And the exact same technology may be what gets us to the finish line for an HIV vaccine, says Steven Deeks, M.D., an HIV specialist, vaccine researcher and professor of medicine at the University of California, San Francisco (UCSF).

An mRNA vaccine works by delivering a piece of genetic material that instructs your body to make a protein fragment of the virus, which your immune system recognizes and remembers, so it can create a robust immune response if it’s exposed to it again. 

“With this technology, we can develop new vaccines and test them much more quickly than we did in the past,” Deeks says. This means researchers will be able to design vaccines rapidly and learn whether they are able to create the broadly neutralizing antibodies required for a successful HIV vaccine.

But the COVID-19 pandemic has also created some hurdles for vaccine development.

“We’ve seen a lot of setbacks in our HIV goals, as resources that could have gone towards HIV vaccine research went towards creating a COVID-19 vaccine instead,” says Monica Gandhi, M.D., professor of medicine and director of the UCSF Center for AIDS Research in San Francisco. In addition, there are concerns that some of the vaccine hesitancy seen during the COVID-19 pandemic could spill over to an HIV vaccine, when one is finally developed, Wessner says. “We saw this with the human papillomavirus vaccine as well,” he says. “There may be a lot of resistance if an HIV vaccine becomes available to the general public.”

Where HIV vaccine research is now

Up until recently, the most promising line of research was investigating whether injecting healthy people with broadly neutralizing antibodies can protect against HIV. Scientists mass-produced one antibody, known as the VRC01 antibody, discovered in the blood of a patient living with HIV.

Initial research suggested that it might be up to 75 percent effective in preventing HIV transmission. But a 2021 study that followed more than 4,000 at-risk people for 20 months found that this antibody was able to block only about 30 percent of the HIV strains circulating in a community.

Nevertheless, “it gave us the green light to look at other ways of antibody development, such as mixing antibodies together to create a cocktail that blocks HIV at different points,” says Stephaun Wallace, a staff scientist in the vaccine and infectious disease division at the Fred Hutch Cancer Center in Seattle and a clinical assistant professor at the University of Washington.  

Despite all of these roadblocks, HIV vaccine research continues to move forward. Here’s a look at a few of the most promising human clinical trials:

HVTN 301. This study, run by the HIV Vaccine Trials Network at the Fred Hutch Cancer Center, uses a tiny protein, or immunogen, to see if it can generate broadly neutralizing antibodies that protect against HIV. The hope is that the immunogen can stimulate the development of a certain type of immune system cell known as B cells, so that they can create the antibodies themselves. 

HVTN 302. This study, funded by the National Institutes of Health, evaluates three experimental HIV vaccines based on the mRNA platform. Each vaccine, created by drug company Moderna, contains a different spike protein found on the surface of the HIV virus that allows it to enter human cells. (None of these vaccines can actually cause HIV infection.) “The amazing thing about the mRNA technology is that it allows your body to make much higher levels of protein, so that it can raise a vigorous immune response,” Gandhi says.

IAVI G002. This is a clinical trial sponsored by the International AIDS Vaccine Initiative, testing the safety and immune response of two mRNA vaccines on 56 healthy adults. Earlier research found that one of the vaccines was able to stimulate the production of rare immune cells needed to create antibodies against the HIV virus in 97 percent of patient participants.

In addition, researchers are studying the use of some of these potential HIV vaccines as a means of treatment. “There is a big push now to cure HIV infection, since it’s hard for many people to get on [antiretroviral] therapy and stay on it for decades and decades,” Deeks says. “The hope is that these vaccines can actually train a person’s immune system to take care of the virus on its own. It would be amazing if some of these vaccines are able to be used not just as a prevention but also as a cure.”

Hallie Levine is a contributing writer and an award-winning medical and health reporter. Her work has appeared in The New York Times, Consumer Reports, Real Simple, Health and Time, among other publications.  

Editor's Note: This article has been updated to correct the trial sponsor of the IAVI G002 study.