An antibody designed to fight HIV that generated excitement last year when it was proven to work well in monkeys has now been shown effective in humans.
The results of a phase 1 clinical trial using antibody 3BNC117 were published today in the journal Nature.
In the trial, researchers injected the antibody into 29 volunteers, 17 with HIV and 12 without. The subjects received one intravenous dose of 1, 3, 10, or 30 milligrams of the antibody.
“Among HIV-infected participants, 3BNC117 had the greatest effect on the eight participants who received the highest dose, resulting in significant and rapid decreases in viral load,” the National Institutes of Health (NIH) reported in a news release. “HIV resistance to 3BNC117 was variable, but some individuals remained sensitive … for 28 days.”
The findings are significant because it’s the first time a “new generation” antibody used to fight HIV has been tested in humans. Study authors also hope the investigational antibody may be used to help wipe out latent HIV that hides in an infected person’s body.
Immunotherapy using antibodies has not been particularly successful for HIV up until now. The first round of antibodies tested, known as “first generation” antibodies, did not prove to be broadly neutralizing, meaning that they could not attack multiple strains of HIV.“What’s special about these antibodies is that they have activity against over 80 percent of HIV strains and they are extremely potent,” said Marina Caskey, lead researcher on the new study, in a news release.
Caskey is an assistant professor of clinical investigation in the Nussenzweig Laboratory of Molecular Immunology at the Howard Hughes Medical Institute at The Rockefeller University in New York City.
Antibody Packs Punch Against 195 of 237 Strains
The antibody 3BNC117 worked against 195 out of 237 HIV strains, making it broadly neutralizing. The antibody targets the CD4 receptor of HIV host cells.
Some subjects receiving the 30 milligram dose experienced 300-fold decreases in their viral load. In some subjects, viral loads remained below the benchmark even after eight weeks. But the virus eventually did begin to mutate to escape the antibody.
“One antibody alone, like one drug alone, will not be sufficient to suppress viral load for a long time because resistance will arise,” Caskey said.
But it does hint that one day antibody therapies may only require a once-quarterly injection.
“In contrast to conventional antiretroviral therapy, antibody-mediated therapy can also engage the patient’s immune cells, which can help to better neutralize the virus,” said co-author Florian Klein, also an assistant professor at the Nussenzweig laboratory.
The Challenge of Bringing Immunotherapy to Scale
In a statement to Healthline, Mitchell Warren, executive director of AVAC, an advocacy group focusing on HIV prevention, said other antibodies also are being studied in human clinical trials, including TMB-355, PG121, and VRC01.
“This latest work is, indeed, exciting, but it is still quite early,” he wrote.
Warren said questions remain about which antibodies to pursue, how to combine them to pack a potent punch, and whether the approach is feasible on a large scale.
“Nussenzweig and colleagues are really on the cutting age of this and we are all keen to see if this concept can be proven — but questions of manufacturing, health system deliverability, and user-demand will be just as important,” Warren said.
That doesn’t mean the research shouldn’t continue, he stressed. “As we know from the history of [antiretroviral drugs, or ARVs], if we had stopped with early concerns about price and feasibility, we would not have nearly 15 million people on ARVs today.”