- A phase 1 clinical trial confirms that the first stage of a novel approach to vaccination is safe and could, in principle, work against HIV.
- The strategy would involve a series of vaccinations that activate and develop a rare type of immune cell.
- In theory, the resulting immune cells could produce antibodies that target an otherwise inaccessible weak spot on the virus’s outer surface.
- Scientists could use the same approach to develop vaccines for other challenging pathogens, such as malaria and the influenza, dengue, Zika, and hepatitis C viruses.
Researchers have taken the first step toward developing a novel type of vaccine regimen that could protect people against HIV.
The virus, which progressively weakens the immune system, affects about 38 million people worldwide.
Highly effective antiviral treatments for HIV are available, but those living with the virus must take them for the rest of their life, and the long-term health effects of infection remain challenging.
In addition, access to prevention and treatment services is limited in some parts of the world.
The World Health Organization (WHO) estimates that, as a result, there were 1.7 million new infections with HIV in 2019, and 690,000 people died from HIV-related causes.
Despite decades of work, scientists have failed to develop an effective vaccine against the virus.
The reason for this is that most of the surface of the virus is densely coated with sugar molecules that do not trigger an immune response, and the parts that are exposed are highly variable.
As with SARS-CoV-2, which is the virus that causes COVID-19, HIV uses spike proteins on its outer surface to gain entry to its host cells.
“The spike protein on HIV viruses is much more devious,” explains William Schief, Ph.D., a professor and immunologist at the Scripps Research Institute in La Jolla, CA, and executive director of the International AIDS Vaccine Initiative (IAVI).
As a result of the rapid mutation of the genes that make the spike, HIV has millions of different strains. Due to this, antibodies against one strain are unlikely to neutralize the others.
“And so HIV is not really one virus,” says Prof. Schief. “It’s really like 50 million different viruses around the world right now.”
However, researchers have known for some time that there are hard-to-access parts of the spike that do not change very much.
Antibodies that bind to these regions are known as broadly neutralizing antibodies (bnAbs) because, in theory, they could target a wide variety of HIV strains.
On rare occasions, people with HIV make these antibodies naturally.
This natural production gives scientists the opportunity to identify where the antibodies bind to the virus. With this knowledge, they can develop “immunogens” to use in vaccines.
The catch is that only a rare type of immature immune cell, known as a naive B cell, can develop into circulating B cells capable of making bnAbs against HIV.
Only about 1 in a million naive B cells have this potential, says Prof. Schief.
To overcome this issue, he and his colleagues at Scripps Research and IAVI used a technique called germline targeting to create a vaccine that activates these rare cells.
In a phase 1 clinical trial, the vaccine appeared to be safe, and it had the desired effect in nearly all of the volunteers who received it.
Researchers at George Washington University in Washington, D.C., and the Fred Hutchinson Cancer Research Center in Seattle, WA, recruited 48 healthy adult volunteers for the trial.
They gave the participants two doses of either the vaccine or a placebo.
The scientists report that the vaccine activated naive B cells in 97% of participants who received it.
“A holy grail of the HIV vaccine field is to elicit broadly neutralizing antibodies by vaccination. And here, we’ve shown in humans that we can start that process,” says Prof. Schief.
He presented the results at a virtual conference of the International AIDS Society HIV Research for Prevention on February 3, 2021.
It is worth noting that the trial was small and that the results have yet to be published in a scientific journal.
In addition, it is important to note that further research and several more clinical trials will be necessary to develop and test later stages in the vaccine regimen.
The vaccine would be only the first in a series of injections to create immunity against the virus.
The first jab would “wake up” the naive B cells, and subsequent jabs would train their descendants to produce bnAbs against HIV.
“We believe this approach will be key to making an HIV vaccine and possibly important for making vaccines against other pathogens,” says Prof. Schief in a press release from Scripps.
He believes that researchers could use the same approach to develop vaccines against other challenging pathogens, such as influenza, dengue, Zika, hepatitis C, and malaria.
The team has now joined forces with the biotech company Moderna to develop an mRNA-based vaccine that targets the same cells.
As it has with the development of COVID-19 vaccines, mRNA technology should accelerate the process of developing the vaccines.