Two studies published back to back in Science show early clinical promise for the development of HIV vaccines that can induce broadly neutralizing antibodies (bnAbs) against the virus, which is considered the holy grail for a preventive HIV vaccine. These studies represent a step forward in the prevention of one of the world’s most deadly infections, second only to tuberculosis.
No vaccine candidate against HIV has been successful in late-stage clinical trials so far. One of the main challenges for vaccine developers is that the virus mutates very quickly, avoiding immunity and resulting in a very high diversity of strains circulating across the world. Unlike other antibodies, which may only recognize a specific HIV variant, bnAbs target parts of the virus that are not affected by mutations.
Both studies have reported encouraging results from vaccines employing a germline targeting approach, where an initial dose of the vaccine is designed to activate a rare type of B cells that are responsible for producing bnABs. Once these cells are primed, their maturation process can be guided to promote the production of stronger, broader targeting antibodies.
Researchers at Amsterdam University Medical Center in the Netherlands and Rockefeller University in the United States reported positive results for a germline targeting vaccine that was evaluated in a Phase I clinical trial enrolling a total of 47 patients. The vaccine is designed to target the CD4 receptor binding site of the envelope glycoprotein trimer of the HIV virus, which makes up the outermost structure of the virus.
“Across the participants we saw an immune response that indicates that we’re on the right track,” said Rogier Sanders, PhD, professor of virology at Amsterdam UMC and senior author of the study. “We saw that we can target the cells that we need to target with atomic precision. The next step is to further stimulate these cells to secrete broadly neutralizing antibodies.”
In another study, researchers at the Scripps Research Institute, the International AIDS Vaccine Initiative (IAVI), and the University of Nairobi reported promising data from two separate Phase I clinical trials that recruited nearly 80 patients across North America and Africa. Both trials evaluated a germline targeting vaccine encoded into mRNA nanoparticles to prime and boost the production of bnAbs. While one of the trials focused solely on the priming stage of the vaccine, showing the vaccine could successfully activate the target immune cells in African populations, the other confirmed that adding a booster dose can advance the maturation of the target cells.
“We’ve now shown in humans that we can initiate the desired immune response with one shot and then drive the response further forward with a different second shot,” said senior author William Schief, professor of immunology and microbiology at Scripps Research; vice president for protein design in infectious disease research at Moderna; and executive director of vaccine design at IAVI’s Neutralizing Antibody Center. “These trials provide proof of concept for a stepwise approach to elicit custom-tailored responses—not just for our vaccine, but for the vaccine field at large, including non-HIV vaccines.”
