The nonprofit International AIDS Vaccine Initiative (IAVI) and the biopharmaceutical company Moderna announced on Jan. 27 a phase-one human trial of “experimental HIV vaccine antigens.”
The trial includes 56 participants in four locations: George Washington University School of Medicine in D.C., the Emory Vaccine Center in Atlanta, the Fred Hutchison Cancer Research Center in Seattle, and the UT-Health Science Center in San Antonio, according to the IAVI announcement.
This is not the first HIV vaccine human trial. IAVI, which is primarily funded by the U.S. and European Union governments and the Bill and Melinda Gates Foundation, has several such trials underway. But this is the first one that involves the messenger-RNA techniques that Moderna and Pfizer-BioNTech made famous last year with their Covid-19 vaccines.
Nearly a billion people received an mRNA-based Covid vaccine last year, including nearly 90 percent of the Americans who were vaccinated. Not many molecules are household names, but mRNA became one in 2021. So, the announcement of an HIV vaccine human trial with an mRNA component resulted in more press attention than these studies typically receive.
Provincetown resident Paolo Martini, the chief scientific officer for rare diseases at Moderna, which is headquartered in Cambridge, enabled an Independent reporter to learn more about the HIV vaccine study by setting up an interview with Sunny Himansu, project leader for HIV efforts at the company. (Martini is also the new owner of the Crown and Anchor in Provincetown.)
Himansu described “germline targeting,” the attempt to stimulate and cultivate the immune system into producing the unusually shaped antibodies that can potentially block HIV infection. (See separate story on the science.) He also put the current study into context: germline targeting is one of several current approaches to an HIV vaccine, and it will take years of testing to identify a series of immune-stimulating proteins that might work.
“This is experimental medicine,” said Himansu. “The purpose of these trials is to iterate: to generate data, and look at the data, and go back and do it again, as many times as possible, until you find a vaccine.
“We don’t really know how far away or how close we are,” Himansu added. “We’re trying to pursue many approaches in parallel, because we don’t know what’s going to work.”
IAVI has been working on this line of research for years, Himansu said. Their partnership with Moderna is meant to help accelerate the testing program.
“Any time you make a drug that is protein-based, that drug requires its own manufacturing facility, tailored to manufacturing that one product,” Himansu said. MRNA molecules for many different proteins can all be made at the same facility, Himansu said. Using mRNA makes a very costly manufacturing process much faster.
Himansu said that a successful germline targeting strategy would likely require a series of four shots, or maybe more. The study happening right now is testing potential candidates for the first and second shots in the series.
In other words, what’s being tested now is not an HIV vaccine itself but the possible eventual components of one. An effective and approved vaccine sequence could still be 10 or 15 years away, Himansu said.
The Geography of HIV
HIV and AIDS have a long and traumatic history in Provincetown. From the earliest days of that epidemic, when it didn’t yet have a medical name and was still being called the “gay plague,” people came here for shelter, care, and dignity. Provincetown was a refuge, but AIDS ravaged and killed here for 15 years before the first successful drug cocktails came out in 1996.
Since then, diverse therapeutics, and the subsequent rollout of pre-exposure prevention pills, or PrEP, have been game-changers, said Dan Gates, CEO of the AIDS Support Group of Cape Cod. He estimates that about 10 percent of Provincetown’s year-round population is now living with HIV.
Although many people outside the gay community are still not aware there’s a pill that can prevent HIV and that is more effective than condoms, said Gates, both the federal and state governments have invested heavily in these drugs — and they are generally free to patients in Massachusetts. Where there aren’t such supports, however, the drug treatments remain very expensive, and HIV is more like its old unconstrained self.
In other corners of the U.S. and the world, and in southern Africa in particular, the need for the vaccine remains urgent. The World Health Organization reports that only 52 percent of HIV patients in Africa know their status and have access to drug therapies, and around nine million have untreated HIV.
“The reality is, HIV has become a killer of the poor,” said Himansu, “both in the most vulnerable populations of the U.S. and globally. The people who need the vaccine are the poorest people, and the poorest nations, who can’t really afford these drug treatments.”
As the world has witnessed during Covid, however, vaccines do not always go to the people and places that need them most. According to the African Union CDC’s Covid dashboard, only 20 percent of the continent is even partly vaccinated against Covid, and only 15 percent is fully vaccinated.
Moderna has come under particular criticism, including from Sen. Elizabeth Warren and the nonprofit Doctors Without Borders, for not directly sharing its technology with African nations, especially after having received federal funds to expedite its Covid vaccine trials and manufacturing plant. On March 8, Moderna announced a preliminary agreement with the government of Kenya to build a vaccine manufacturing plant there.
The HIV vaccine is on a different path, however. The candidates being tested now belong to IAVI — the proteins being delivered to the body via mRNA were developed over years of research by Prof. William Schief of the initiative’s Neutralizing Antibody Center. The trial itself is being paid for by the Gates Foundation.
Production is where Moderna’s contribution comes in. “We’ve been able to expedite production of clinical trial material at a remarkably rapid pace because of Moderna’s technology,” said Schief.
“Bill Schief is the one who invented this,” said Himansu. “We’re doing these partnerships, making our technology accessible so people can find and discover a vaccine. At the end of the day, they can make these independently in the future, with or without Moderna.”