The Dream of HIV Vaccines May Finally Be Coming True

HIV destroys the immune system from within. Despite decades of research, there still isn’t a vaccine against the virus. The shape-shifting pathogen rapidly adapts to vaccines and renders them useless. And HIV-blocking drugs are expensive to produce, test, and ship, stifling their impact around the world.

But inspired by Covid, two studies are changing the vaccine recipe. The new vaccines include mRNA molecules encoding the protein “stem” of HIV—a part of the virus that doesn’t mutate as fast. Cells produce the protein, and this warns the immune system. When injected into rabbits and monkeys, two versions of the vaccine triggered an antibody avalanche against HIV.

The vaccines were also shown to be safe in an early trial in healthy human volunteers. After three doses several weeks apart, up to 80 percent of the participants produced HIV-blocking antibodies. A few people developed minor but uncomfortable side effects, including hives and rashes, which lasted months or even years in some.

While not yet perfect, the vaccines are relatively easy to distribute and administer. They also shed light on how different versions of the protein impact immunity: A membrane-bound type was especially promising. The results “should assist HIV vaccine development,” wrote study author William Schief and team at the Scripps Research Institute.

Viral Enigma

HIV has perplexed scientists since it first emerged in the 1980s. After health officials noted a striking rise in pneumonia and cancers in previously healthy young men, labs eventually isolated HIV as the main antagonist.

The virus destroys multiple types of immune cells that protect us from infection. Roughly speaking, we have two main immune warriors: T cells grab onto invading pathogens or cancer cells and wipe them out, while B cells pump out antibodies.

HIV throttles these defense mechanisms, allowing other diseases to thrive. Before the turn of the century, a simple respiratory infection could be lethal to a person with HIV. But thanks to antiviral drugs, AIDS, the disease that HIV causes, is no longer a death sentence. And PrEP was approved as a prophylaxis over a decade ago. In 2025, the FDA approved the first HIV-prevention drug needing only two injections every year. It completely prevented at-risk women in sub-Saharan Africa from infection for up to six months.  

Other prevention efforts have borrowed a genetic hack. Some people are genetically resistant to the virus. Transplanting blood stem cells from these people can reproduce their immunity in those already infected. Last year, a 60-year-old man in Germany living with HIV became the seventh person to be free of the virus for almost six years after transplant.   

These strategies have weaknesses though. A full stem-cell transplant requires wiping out existing cells, which takes a toll on an already fragile body. A daily pill is more practical, but people need dependable access to a steady supply.

One Powerful Jab

The new studies tap mRNA vaccine technology to build an alternative to existing solutions.

These vaccines encode segments of a pathogen into mRNA molecules and shuttle them into cells. Cells use the mRNA to produce a small piece of the virus, which teaches the immune system to recognize it as an invader. When infected with the real thing—viruses that cause disease—the body produces antibodies to neutralize it. In HIV, this same strategy protects immune cells from being invaded by the virus and keeps our bodies ready for combat.

The HIV virus has a protective enclosure called an envelope, which contains a protein called Env. Some versions of the protein are soluble and drift into the bloodstream. Others are tethered to the virus and cell membrane. Previous HIV vaccine candidates targeted Env’s “stem” with antibodies. The problem is, the stem can be hidden from antibodies inside the viral membrane.

Other candidates engineered mRNA molecules that instructed cells to make two chunks of the Env protein and increase the immune response. In HIV-infected mice, the mRNA vaccine designed to target those bits of Env spurred the production of antibodies.

The two new studies took this a step further. One encoded both soluble and membrane-bound forms of the Env protein. When injected into the leg muscles of rabbits, the animals developed antibodies to the proteins for up to 24 weeks. Of the two, the membrane-bound version far more effective. In monkeys, the vaccine slashed HIV levels for 26 weeks, and boosted the animals’ B cell response. The immune cells also developed a reservoir of “memory” cells that activate in the presence of another HIV infection.

A Small Step

Encouraged by the results, a second team tested both versions of the vaccine in 108 healthy people. The Phase 1 trial mainly studied safety, but it also monitored the antibody response in volunteers aged 18 to 55 across 10 sites in the US.

Each volunteer received three jabs of a single vaccine at different doses. Like the results in rabbits and monkeys, the protein’s membrane-bound version was more efficient and blocked HIV in nearly 80 percent of people. Soluble versions didn’t do as well, with only four percent of participants generating antibodies.

“The difference is pretty striking,” Sharon Lewin, at the Peter Doherty Institute for Infection and Immunity, who wasn’t involved in the study, told Nature.

The vaccine was mostly easy on the body. But roughly 6.5 percent of participants broke out in large rashes regardless of dose, and some of these lingered for years. The response could be due to a combination of HIV infection and mRNA side effects. The teams are still working out the exact mechanism causing the rashes and ways to combat it.

With almost 41 million people living with HIV globally, the side effect is a manageable bump on the road. “The need for an HIV vaccine is high,” Lewin told Nature.