Back in 2016, Dr. Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, was bullish about HVTN 702, a potential vaccine for the human immunodeficiency virus.
“If deployed alongside our current armory of proven HIV prevention tools, a safe and effective vaccine could be the final nail in the coffin for HIV,” Fauci said about a trial of the vaccine.
But by 2020, the trial for HTVN 702 had been discontinued because it was unable to prevent HIV infection. Thus far, no HIV vaccine has proven to be successful. That is due to the nature of the virus and the limits of vaccine technology.
But that may change, thanks to messenger RNA. The same technology that is being used in the Pfizer and Moderna COVID-19 vaccines may eventually result in an HIV vaccine.
“There should be renewed interest in an HIV vaccine, given the experience with the COVID vaccine,” said Wim Tiest, director of infectious disease programs at eTheRNA Immunotherapies, a company based in Belgium that specializes in mRNA technology.
HIV is the virus that, of course, causes AIDS. An estimated 32 million people have died from AIDS worldwide since the epidemic began in the 1980s. About 38 million people worldwide and approximately 1.2 million in the United States are infected with HIV.
Until recently, most vaccines worked by introducing a dead version of a virus into a person’s body to imitate an infection. This would train the immune system to create antibodies designed to target the virus, should it invade that person’s body. The antibodies work by attacking the specific proteins on the surface of a virus. However, if those proteins change, then the antibodies are rendered ineffective.
One reason that no HIV vaccine has thus far been effective is that HIV mutates so rapidly, constantly changing the proteins on its surface.
“What viruses can do fairly well is change their surface,” Tiest said. “But every virus has parts that it cannot change.”
Therein lies the promise of an mRNA-based vaccine. The link in a cell between a cell’s DNA and its proteins is the mRNA. The DNA stores the genetic instructions that a cell needs to make proteins, and the mRNA sends the instructions from the DNA to ribosomes, the machinery in a cell that produces proteins.
Most importantly for purposes of an HIV vaccine, mRNA does not mutate.
“By using mRNA, a vaccine can elicit antibodies that recognize not just one specific version of a virus, but a whole range,” Tiest said. “These are called ‘broadly neutralizing antibodies,’ which are ones that can recognize a virus even if it starts to change.”
Scientists have known about broadly neutralizing antibodies since the 1990s, when they were found in AIDS survivors. More recently, IAVI and Scripps Research have collaborated to develop an HIV vaccine that creates such antibodies. IAVI is a New York-based nonprofit organization that focuses on vaccine development, while Scripps Research, a California-based nonprofit organization, focuses on biomedical science. They developed a vaccine that they hoped would create a rare type of immune cell known as an IgG B cell. An IgG B cell is the one that can produce broadly neutralizing antibodies.
Thus far, the results of the IAVI-Scripps vaccine have been promising. In a small trial involving 48 people, IgG B cells were produced in 97% of those who received the vaccine.
“This study demonstrates proof of principle for a new vaccine concept for HIV, a concept that could be applied to other pathogens, as well,” said William Schief, a professor and immunologist at Scripps Research and the executive director of vaccine design at IAVI’s Neutralizing Antibody Center.
However, the IAVI-Scripps vaccine did not use the far more promising technology of mRNA. That will soon change, as IAVI and Scripps Research have announced that they will be partnering with Moderna to produce an mRNA-based HIV vaccine that can develop IgG B cells and broadly neutralizing antibodies.
While the future may look bright for an HIV vaccine, Tiest warns that a widely available vaccine may still be years down the road.
“I think interest in HIV has declined because there is treatment. Now, we can put someone on therapy, and that person can have a normal life, so where’s the urgency?” Tiest said.
In the last 20 years, medicine has developed a regimen of drugs to treat HIV known as antiretroviral therapy. That therapy reduces the amount of HIV in the body and gives the immune system a chance to recover.
Tiest said he thinks that the lack of urgency will mean that an HIV vaccine will not be a high priority.
“Will the world wake up tomorrow and put the same effort into HIV as it put into COVID? I don’t think so,” Tiest said. “COVID has shown us that with more resources and more effort, [vaccine development] can go faster. But I don’t think HIV will become the No. 1 priority for world health tomorrow.”
