The key to developing a new drug to fight HIV may lie in the blood of a patient whose immune system can control the infection, a new study says. Scientists discovered proteins in the patient’s blood that blocked the virus from infecting immune cells. Researchers hope to harness these proteins not only to treat the virus, but to help develop a vaccine.
HIV is such a dangerous virus because it attacks the very cells that would normally fight it off, called T cells. These cells protect the body against infections, and when an HIV patient’s T cells drop to dangerously low levels, the patient is said to have progressed to AIDS; AIDS patients typically die of secondary infections the body is too weak to fight off.
That’s why this patient, called Z258, is so important: his body has a natural immunity to the virus. His immunity is a little different than the famous Berlin Patient, who received a bone marrow transplant from someone who has T cells HIV can’t bind to — and thus can’t infect. Instead, patient Z258’s blood contained immune proteins called antibodies that block the virus from infecting cells, and they can neutralize a whopping 98 percent of the de-clawed HIV virus strains the scientists generated in the lab. These antibodies could even block strains that other, similar antibodies were powerless against. Even though HIV was detectable in his blood and he wasn’t being treated at the time, this patient had normal T cell levels after more than two decades of infection. The researchers named the antibody N6 in their findings published this week in the journal Immunity.
“It is an important step, it’s very interesting scientifically,” says Lars Hangartner, an immunologist at the Scripps Research Institute. While experiments with antibody therapies haven’t completely cleared primates’ bodies of HIV, understanding how the body generates effective neutralizing antibodies could help with designing vaccines. And antibodies could be useful preventative treatments if someone suspects they’ve been exposed to HIV, he says.
Antibodies that successfully neutralize HIV are rare, because antibodies need to recognize specific patterns on the virus in order to target it. HIV mutates so rapidly that those patterns constantly shift and change even within a single individual — which lets the virus evade the antibodies hunting it. That’s not all. HIV has proteins on its surface that can push antibodies away. The combination of these two factors makes it difficult for the body to mount a defense against the virus — and for scientists to develop an antibody therapy that’s as strong and as broadly effective as current antiretroviral drugs.
“We didn’t think that there were people out there that had broadly neutralizing antibodies against HIV because of its diversity,” says Mark Connors, an immunologist at the National Institutes of Allergy and Infectious Diseases and the lead author of the study. “So it took screening to find those patients, and then within those patients, special techniques to screen for antibodies that showed us how those patients do it.”
These screens turned up a few patients with antibodies effective against HIV in the past, and scientists are developing these antibodies as medicines to treat HIV or even to prevent an infection from taking hold, kind of like a preventative antiviral drug regimen currently on the market called PrEP. But this patient’s blood contained an antibody that was particularly powerful. That’s because it targeted part of a protein on HIV’s surface that sticks to, and infects, T cells. This protein usually doesn’t change much as HIV mutates and evolves, and even when it does the antibody ignored the tweaks to its target and continued to stick to it.
The advantage of an antibody drug is that antibodies stick around in the blood for longer than current antiretrovirals, which means patients wouldn’t have to take them as often. But current antiretroviral drugs are really good — so anything new that comes on the scene would have to be as strong and as difficult for the virus to evolve resistance against. Biologics are also notoriously expensive.
Because HIV mutates so rapidly, it’s also possible the virus could evolve to resist an antibody therapy. “Single antibodies are unlikely to work because, even probably against N6, [HIV] can develop resistance,” Connors says. But he does envision adding an antibody cocktail to current antiretroviral drugs to help patients fight off the virus even more effectively. This discovery isn’t a fast track to a cure — but these findings could add another weapon to a clinician’s arsenal against a virus that had once been a death sentence.