Engineered Antibodies Block HIV Infection in Primates for 6 Months
In the absence of an HIV vaccine, a single injection of engineered antibodies could block new infections in at-risk populations for months at a time.
Despite more than 30 years of HIV research, there’s still no vaccine for the immune-targeting virus. If left untreated by antiretroviral therapies, HIV results in full-blown AIDS, a total collapse of the immune system, which has claimed 35 million lives since the HIV/AIDS epidemic first began in the 1980s.
While a lifelong HIV vaccine remains elusive, exciting progress has been made with a class of antibodies that appear to protect against HIV infection for weeks at a time. And now a team of researchers working with new, lab-mutated versions of these antibodies has reported that a single injection of their altered antibody protected monkeys from HIV infection for an average of more than six months — and in some cases as long as 8.5 months.
HIV is different than other viruses in that it mutates as it makes copies of itself inside the body. These mutations make it almost impossible for the body’s immune system to create a single antibody that’s effective against the constantly changing strains. Vaccines usually work by triggering the body to create the right antibody to kill off the disease. But in the case of HIV, scientists have had to explore new approaches.
Back in 2010, researchers at the National Institute of Allergy and Infectious Diseases (NIAID) isolated antibodies from a remarkable individual who had lived with HIV for 10 years without any treatment or any symptoms of the disease. It turns out that in rare cases, people living for years with HIV develop what’s called broadly neutralizing antibodies (bNAbs).
While it’s too late to reverse the infection in those individuals, researchers wondered if the bNAbs could be cloned in the lab and used to protect uninfected individuals.
In initial lab tests, a handful of bNAb strains showed the uncanny ability to block new infections from 90 percent of all global HIV strains.
One of these bNAbs, a strain called VRC01, is already being tested on humans as part of a Phase 2 clinical trial that includes participants in five sub-Saharan African nations, where 70 percent of the world’s current HIV-positive population is found.
If bNAbs effectively block HIV in people, they could provide a life-saving prophylactic treatment in the absence of a permanent vaccine. However, one of the drawbacks of prophylactic injections with VRC01 is that the protection only lasts for eight weeks, after which you need a new injection to keep the antibodies in the bloodstream.
In a new study published in Nature Medicine, researchers Michel Nussenzweig of Rockefeller University and Malcolm Martin at the NIAID genetically engineered new strains of two other bNAbs that appear to dramatically extend the time between protective injections. One engineered antibody protected six macaque monkeys from HIV infection for a median of 27 weeks, which was more than two times longer than the original strain. One animal remained infection-free 37 weeks after injection.
As part of the experiment, 12 monkeys were injected with engineered strains of two different bNAbs, 3BNC117 and 10-1074. The macaques were then “challenged” with weekly exposure to simian-HIV (SHIV), a lab-engineered version of human HIV for monkeys. When untreated macaques were exposed to the same weekly dose of the virus, they tested positive for SHIV in an average of three weeks.
The treated monkeys, however, remained infection-free for a median of 17 weeks for the engineered 3BNC117 and an impressive 27 weeks with the engineered 10-1074. In the case of the engineered 10-1074, that was 2.2 times longer than the 12.5 weeks achieved by the original 10-1074 strain.
Anthony Fauci, director of the NIAID and a veteran HIV researcher, told Seeker than Nussenzweig and Martin’s paper was “a really important proof of concept.”
“HIV is so problematic with regard to a vaccine that it’s forcing us to try and pursue these alternative strategies,” said Fauci. “Theoretically, [treatment with engineered bNAbs] could serve as a very effective way to prevent infection without necessarily having to get a vaccine to induce the antibody.”
The researchers are hopeful that the positive macaque results will be replicated in humans and plans are underway for Phase 1 clinical trials. One potential complication is that the macaque experiments used a single, cloned strain of SHIV, while human HIV in the “wild” is much more genetically diverse.
For that reason, explained Fauci, the researchers experimented with different combinations and concentrations of 3BNC117 and 10-1074 together in the same injection, and more trials are needed with other combinations of bNAbs.
“If you treat subjects with two or three antibodies, then the chances of the diverse virus escaping from the protection are much less than if you only have a single antibody,” said Fauci. “Ultimately, when all the studies are done, we’re going to pick out the best two or three or four and use them as a standard regimen of protection.”
Beyond the efficacy of the protective HIV injections, there’s also the issue of cost. Right now, it’s still very expensive to engineer large quantities of these antibodies, and the regions with the greatest need are also some of the world’s poorest.
“If these antibodies are going to be used, they’ll have to achieve an economy of scale to get it down to a reasonable price,” said Fauci. “You can’t have an antibody that costs $100,000 a year. Obviously, that’s not going to work.”