In addition to developing and manufacturing synthetic drugs to treat and prevent HIV, researchers are working on ways to use our own immune systems to fight and prevent HIV infection. Broadly neutralizing antibodies, which are produced by the immune system of some people living with HIV, may be part of one such strategy.
In a CROI session today (February 13) about advances in antibody treatments for HIV prevention and treatment, Richard Kroup, MD, from NIAID provided an overview of the recent advances in the field—and what antibodies could mean for future vaccine and HIV treatment options.
“I like to think there’s a reasonable likelihood that antibodies will work [for prevention],” said Koup. “There’s a good safety record with monoclonal antibodies for other targets, and the potential that a single shot could confer long-lasting protection for three to six months.”
A total of 23 broadly neutralizing HIV antibodies have been discovered since 2009, said Koup, which have different target binding sites on virus particles. This boom in discovery provides hope for scientists, who are now trying to figure out how to increase the potency (how well the antibodies protect against HIV) and breadth (how many strains of HIV antibodies provide protection against) of these antibodies.
Although, explained Koup, antibodies used for prevention won’t need as much potency and breadth as those used for treatment.
“The bar for prevention is much lower,” said Koup. “For prevention, you probably only need to block the one or two viruses that get transmitted. So there’s less requirement for potency and breadth—a lower threshold for success. For treatment, you have this vast quasi-species which has been constantly adapting to the neutralizing antibodies that are developing in that individual. So you’re going to need much more potency and breadth in a treatment protocol.”
Making antibody treatments more powerful
Broadly neutralizing antibodies used one at a time will not be enough to prevent HIV infection or keep virus suppressed in someone living with HIV. But using combinations of different antibodies all at once can increase their power and coverage, said Koup.
Citing a study by Kong and colleagues published in the Journal of Virology in 2015, Koup showed how combinations of four different antibodies (VRC07, PG9, PGT 128 and 10E8) increased protection against HIV.
Using more than two at the same time increased coverage to over 98%. “And any three combinations, and any four combinations—you’re getting a very potent and broad combination,” said Koup.
Koup also explained that a technique developed by the pharmaceutical industry—called cross-Mab technology—may also increase the potency and breadth of antibodies.
Antibody therapies in the clinic for prevention
For more than 20 years, passive antibodies have been tested in non-human primates, explained Koup. “But despite all of this basic science information in non-human primate models, there’s really no human data on passive human protection by HIV-1 monoclonal antibodies,” he said.
The AMP (antibody mediated prevention) study will be the first study to provide answers about antibodies used for HIV prevention. In the study, conducted by HPTN and HVTN, 2,400 men who have sex with men in North and South America and 1,500 women in sub-Saharan Africa will receive a monoclonal antibody (VRC01) HIV-prevention therapy. The antibody is administered through an under the skin injection, every two months. Two different doses are being tested.
“Can antibodies prevent HIV infection in humans? Hopefully the AMP trial will give us some answers there, and at what level of monoclonal antibody is needed to protect,” said Koup.
Antibody therapies in the clinic for treatment
Antibodies could be used during very early HIV infection, said Koup, to rapidly reduce viremia and limit the establishment of the viral reservoir. Broadly neutralizing antibodies could also potentially be used in combination with long-acting antiretrovirals (if approved for treatment) once every two to three months (thanks to their long half-life). Or, they could potentially be used to help clear the viral reservoir.
“We certainly know that antibodies work therapeutically in animal models,” said Koup. “But nicely, we also have data on the effects of monoclonal antibodies in multiple different phase I clinical trials.”
Published two years ago, a study of the antibody 3BNC117 showed that when given to people who were viremic, the antibody was able to suppress viral loads for about 14 days. Another study by Lynch and colleagues, published in 2015, tested the antibody VRC01 with eight people living with HIV. This study had similar findings—the antibody was given, and was able to suppress viral loads for a period of time. Just two weeks ago, Schools and colleagues published a study of the antibody 10-1074 showing that it can suppress virus in people living with HIV.
More options is better
Responding to a question posed by an audience member, Koup explained that monoclonal antibody therapies are important for researchers to pursue as an addition—not replacement—for ARVs.
“Having more options in the armamentarium is always good. I don’t even know the number of ARVs we currently have—but we need all of them. Developing more, to make sure we have something that works, is going to be needed,” he said.
By Emily Newman