On the first day of December, World AIDS Day, a team of researchers behind an HIV vaccine trial published exciting results in Science. Their findings signaled a significant advance in the quest for a vaccine that could eventually protect humanity from a virus without a cure that still infects more than a million people each year. That vaccine remains beyond the horizon, but the researchers were able to crack a puzzle that’s been stumping scientists since the 1990s.
The trial proved that an HIV vaccine candidate could prime broadly neutralizing antibody precursors, using a germline-targeting approach. But unless you’re a specific kind of scientist, those words won’t mean much—we’ll break it down.
First, Broadly neutralizing antibodies. Antibodies are proteins that patrol your bloodstream for pathogens. Broadly neutralizing antibodies are a specific variety of antibodies that are effective against HIV. “A certain percentage of individuals, when infected, mount broadly neutralizing antibodies,” says James Kublin, executive director of the HIV Vaccine Trials Network at the Fred Hutchinson Cancer Center, which was a site of the clinical trials published. In those cases, broadly neutralizing antibodies aren’t enough to cure the individual, but they are part of a body response that has drawn the attention of HIV researchers.
Precursors are elusive cells whose fate in the human body has yet not been decided. They’re like blank key templates, circulating through your body, that haven’t yet been shaved into the shape of a specific lock. In this case, researchers are working to shave precursors into broadly neutralizing antibodies, keys which would be specifically effective against an HIV infection.
Now for the germline-approach: The HIV vaccine candidate researchers have zeroed in on a vaccine candidate that engages the precursors, “targeting those precursors in such a way that it will push them to mature into broadly neutralizing antibodies,” says Dr. Kublin.
That brings us to the trial’s revelations: The vaccine candidate in the trial was able to link up with the precursors. “Now the trick is to find a way to push those precursors to evolve into the specific broadly neutralizing antibody that will unlock that key to preventing HIV,” says Dr. Kublin. In other words, a vaccine compatible with the precursors still needs to spur them to blossom into something able to fight HIV.
Still, the results of the most recent trial show early promise. Of 36 trial participants, the vaccine candidate was able to produce precursors of broadly neutralizing antibodies in 35 individuals. According to Dr. Kublin, around 10 clinical trials slated for 2023 are aimed at advancing the broadly neutralizing antibody strategy at halting the spread of HIV. What’s more, influencing the form that antibodies take can help medicine take on a whole host of “viruses with high antigenic diversity such as HIV, influenza, hepatitis C virus, and betacoronaviruses,” wrote the researchers behind the study.
And while HIV research remains in the stage 1 realm of clinical trials, other advances suggest that timelines to a cure may shorten. The mRNA vaccine technology that helped produce COVID-19 protections at warp speed may also play a role in tackling HIV. Earlier this year, the NIH launched clinical trials of three potential HIV vaccines harnessing mRNA technology. Those trials remain ongoing.
While a vaccine remains years off, experts consider it the keystone to fully addressing the AIDs epidemic. “The control of an infectious disease pandemic according to all of our experiences so far does rely on there being an effective preventive vaccine,” says Dr. Kublin. “After all of these decades, there’s still no HIV vaccine.”