NEW YORK (HealthDay News) – It is thought that for an HIV vaccine to be broadly effective it would have to cause the body to produce special antibodies that can neutralize a wide variety of strains.
Scientists say they have taken a major step in that direction.
Researchers have found that an experimental HIV vaccine was able to induce an immune response needed to produce neutralizing antibodies against the virus. This is the first time a vaccine has achieved this in humans.
The findings, which were published in the Dec. 2 issue of the journal Science, come from a study of 48 healthy adults who received two doses of the vaccine or two of a placebo. Of the 36 participants who received the vaccine, 35 showed a substantial increase in rare immune system cells, precursors to neutralizing antibodies against HIV.
Experts have stressed that the result is a “proof of concept,” meaning that it is possible for a vaccine to induce such a response.
“This is a positive result,” says Colleen Kelley, MD, an associate professor at Emory University School of Medicine and vice chair of the HIV Medicine Association board of directors.
Kelley, who was not involved in the study, says stem cell induction is a “first step.” The question now is whether these precursors can be coaxed into broadly neutralizing antibodies.
Scientists have been trying to develop an HIV vaccine since the 1980s, and there have been glimmers of hope followed by disappointment. HIV is a formidable enemy for many reasons, one of which is its ability to mutate rapidly, spawning new strains as it passes from person to person.
Traditional vaccines against viral diseases, such as measles, flu or Covid, work by stimulating the immune system to produce antibodies against the virus. Antibodies are specialized proteins that recognize foreign invaders, bind to them, and neutralize them.
The traditional method of vaccination hasn’t worked against HIV, Kelley explains. Researchers have successfully developed vaccines that generate antibodies, but those antibodies have not prevented HIV infection.
“We haven’t been able to develop an HIV vaccine because it’s really, really hard,” said Dr. Juliana McElrath, a professor at the Fred Hutchinson Cancer Center in Seattle and an investigator on the study.
progress
More than a decade ago, scientists discovered that some people with HIV are able to produce bnAb against the virus. In the laboratory, these bnAbs can neutralize a wide variety of HIV strains, because they recognize particular proteins that are typically conserved even when the virus mutates.
The problem is that the immune system generally doesn’t produce bnAbs when HIV invades the body. So the next question for the researchers is whether vaccination can induce production.
After years of research into exactly how bnAbs interact with HIV, scientists have created a new generation of vaccine candidates that are in various stages of development.
The new study tested one of these, called OD-GT8 60mer. It is an immunogen, a substance that elicits a modified immune response. It is designed to stimulate and amplify certain rare B cells that have the potential to produce bnAb to fight HIV.
Among the 36 volunteers who received the vaccine, there were no safety concerns. And all but one showed the immune response the researchers were looking for. This is a necessary first step, both McElrath and Kelley point out.
But it is only the first step of a complex process.
“This vaccine kicks things off,” McElrath says. Continuing to drive these precursor cells to mature into HIV-protective bnAb will require several stimuli.
The researchers are now conducting another small study in healthy volunteers, this time evaluating eOD-GT8 60mer followed by boosting with a different immunogen, to provide further insight into the maturation of bnAb precursors.
After decades of searching for an HIV vaccine, the bnAb method represents “a new path,” says Kelley. And there are reasons for cautious optimism, according to McElrath.
“I think this is significant progress from where we were before,” he says. “This provides us with a way forward.”
The research was funded by the Bill and Melissa Gates Foundation, the International AIDS Vaccine Initiative, the US National Institute of Allergy and Infectious Diseases, and others.
