It was like something out of science fiction.
In a 2023 study, a group of macaques, a type of monkey, were given a preliminary HIV vaccine. It was one of many studies in the Duke Human Vaccine Institute’s 19-year quest for a vaccine for the virus that causes AIDS. Kevin Saunders’ team felt good about their results. Once they looked closer, this turned to excitement. At the atomic level, their precisely designed antibody was blocking HIV from binding to the primates’ cells (and, as the team would later see, human cells). That level of precision was a feat. It was like something out of a movie.
“The aha moment was when we actually looked at how the antibody bound to the HIV envelope using electron microscopy,” says Saunders, director of research at DHVI. “Down to the molecular level, this antibody looked very much like what we were going for.”
It’s one of two giant steps DHVI has taken recently toward the elusive HIV vaccine. Barton Haynes, DHVI’s director, feels like a prototype vaccine is tantalizingly close – perhaps two years away, he ventures. (Saunders won’t put a timeframe on it, although he’s just as excited). Indeed, even with modern therapeutics, HIV is the king of tricky diseases. Once a person is infected, HIV enters their genetic material within 72 hours, vanishing from the immune system’s radar in no time at all.
Now DHVI has not one, but two vaccine approaches showing strong promise, and human clinical trials starting soon. The idea: Attack HIV with both at once.
“If we can solve this problem, which we eventually will, then we'll be able to engineer the immune system for the 500 different autoimmune diseases.”
Dr. Barton Haynes
“If we can solve this problem, which we eventually will, then we'll be able to engineer the immune system for the 500 different autoimmune diseases,” Haynes says.
Familiar vaccines like those for measles, mumps and polio were made with the outer coating of a virus or a killed whole virus. In these cases, the immune system recognized the virus’s vulnerabilities and made effective antibodies. Not so with ever-mutating, quick-infecting HIV. Killed virus vaccines would not work.
DHVI undertook the painstaking, years-long work of understanding how HIV evades and fools the human immune system. This led, too, to studying precisely how vaccines work – research that hadn’t been done, Haynes notes, because previous vaccines had been effective without scientists having to design them from the ground up.
“We’ve figured out roadblock after roadblock,” Haynes says.
While Haynes’ HIV research dates to a 1984 paper on the virus, HIV vaccine efforts were largely piecemeal until 2005. That year, the National Institute of Allergy and Infectious Diseases awarded DHVI $350 million – the first of several major grants – to develop the vaccine. This is when DHVI became a true powerhouse.
First came seven years of following hundreds of people infected with HIV. Inside each person there is an arms race between HIV and that person’s immune system. HIV is notorious for dodging multiple immune responses, eventually wearing a person’s system down and infecting them. DHVI researchers noted rare individuals living with HIV who eventually made potent antibodies that could neutralize the virus. These are vanishingly rare antibodies, Haynes says, that are accordingly difficult to induce the body to make.
“You're going to have to get the body to make antibodies that it normally does not make,” says Saunders.
For the other giant step, DHVI is developing a vaccine that induces several unlikely antibodies, arming a person for every twist and turn of the HIV arms race within their body. A vaccinated person would be able to fight the virus off and not get infected. In a clinical trial designed to start the lineages of these antibodies, pending publication in the journal Cell as of press time, volunteers made rare antibodies that neutralized many different HIV strains.
“That’s never been done in humans before,” says Haynes.
DHVI has now developed not one, but two vaccine approaches, Saunders says. To battle the king of tricky diseases, Saunders describes a vaccine using both recent developments to basically carpet-bomb the virus.
“We’ve got to come at it from different angles,” Saunders says.
Getting to this point has taken four decades of diligent research. Haynes has spent most of his career locking horns with a near-impossible foe, which he reflects upon with a sudden roaring laugh.
“That means I’m an optimist, and an incurable one as well,” he says.