Antibody combination puts HIV on the ropes

January 25, 2017, Rockefeller University
HIV infecting a human cell. Credit: NIH

Without antiretroviral drug treatment, the majority of people infected with HIV ultimately develop AIDS, as the virus changes and evolves beyond the body's ability to control it. But a small group of infected individuals—called elite controllers—possess immune systems capable of defeating the virus. They accomplish this by manufacturing broadly neutralizing antibodies, which can take down multiple forms of HIV.

Now a study using antibodies from one of these elite controllers has shown that a combination of three such antibodies can completely suppress the virus in HIV-infected mice. The findings, from the laboratory of Michel Nussenzweig, who is Zanvil A. Cohn and Ralph M. Steinman Professor at Rockefeller University and head of the Laboratory of Molecular Immunology, are being reported in Science Translational Medicine.

"Some people with HIV produce these antibodies, but most of the time the virus eventually escapes them through mutations in the antibody's corresponding epitope," says postdoctoral fellow Natalia Freund, the study's first author. The epitope is the part of the virus that antibodies recognize and attach themselves to, and this ability to mutate makes HIV particularly tricky to tame. It ensures that once the virus is in their bodies, people remain infected forever, and this may be the biggest roadblock in developing immune therapies to overcome the virus.

Tug of war

"Think of the relationship between the antibodies and the virus as an that goes on and on," Freund says. "By mutating, some of the virus may escape the antibodies and continue growing. Years later, the body may produce new against the escaped virus, which in turn may mutate and escape yet again."

"What we've shown in this study is that after several rounds of escape from these particular antibodies, the virus seems to run out of options," she adds. "In this particular case, HIV eventually loses this arms race."

An elite controller's immune system can defeat the virus by coming up with new broadly , and also by producing cytotoxic T cells—immune cells that can recognize and destroy infected cells to immobilize the virus. The patient whose HIV response created antibodies for the study has been working with the Rockefeller team for ten years, contributing his blood serum for their research. He was infected at least three decades ago, and has developed three different types of broadly neutralizing antibodies that bind to three different sites on the virus.

The remarkable thing about his antibodies is that they seem to complement each other's activity, completely shutting down HIV.

The investigators gave the three antibodies, called BG18, NC37, and BG1, to HIV-infected mice whose immune systems had been modified to more closely resemble those of humans. They found that the trio rendered the undetectable in two-thirds of the mice three weeks after it was administered.

"This study validates the approach of using three different to control HIV infection," Freund concludes, "pointing the way toward a potential new treatment for people infected with HIV."

Explore further: Scientists identify immunological profiles of people who make powerful HIV antibodies

More information: Natalia T. Freund et al, Coexistence of potent HIV-1 broadly neutralizing antibodies and antibody-sensitive viruses in a viremic controller, Science Translational Medicine (2017). DOI: 10.1126/scitranslmed.aal2144

Related Stories

Scientists identify immunological profiles of people who make powerful HIV antibodies

July 29, 2016
One of the main mysteries confounding development of an HIV vaccine is why some people infected with the virus make the desired antibodies after several years, but a vaccine can't seem to induce the same response.

Researchers identify potent antibodies against HIV

April 6, 2016
It's been known for some time that the immune system can produce antibodies capable of "neutralizing" HIV, and stopping the AIDS-causing virus dead in its tracks.

Broadly neutralizing HIV antibodies pave the way for vaccine

September 26, 2016
A small number of people infected with HIV produce antibodies with an amazing effect: Not only are the antibodies directed against the own virus strain, but also against different sub-types of HIV that circulate worldwide. ...

Antibodies from unconventional B cells less likely to neutralize HIV, study finds

March 17, 2016
Antibodies derived from a type of immune cell found in unusually high numbers in HIV-infected individuals with chronically uncontrolled virus levels are less effective at neutralizing HIV than antibodies derived from a different ...

Researchers use antibody treatment to protect humanized mice from HIV

February 11, 2014
NIH-funded scientists have shown that boosting the production of certain broadly neutralizing antibodies can protect humanized mice from both intravenous and vaginal infection with HIV. Humanized mice have immune systems ...

Recommended for you

Researchers unravel why people with HIV suffer from more neurologic diseases

August 20, 2018
Human immunodeficiency virus (HIV) and acquired immunodeficiency syndrome (AIDS), which the HIV virus can cause, continue to be one of the world's greatest health problems.

New HIV therapy reduces virus, boosts immunity in drug-resistant patients

August 15, 2018
In a study, a new HIV drug reduced viral replication and increased immune cells in individuals with advanced, drug-resistant HIV infection. Used in combination with existing HIV medications, the drug is a promising strategy ...

In choosing care, HIV patients in Zambia prefer kindness over convenience

August 15, 2018
As a healthcare patient, what would you sacrifice for a provider with a nice—rather than rude—attitude? For HIV patients in Zambia, the answer may surprise you.

Details of HIV-1 structure open door for potential therapies

August 9, 2018
New research provides details of how the structure of the HIV-1 virus is assembled, findings that offer potential new targets for treatment.

Researchers uncover potential new drug targets in the fight against HIV

August 7, 2018
Johns Hopkins scientists report they have identified two potential new drug targets for the treatment of HIV. The finding is from results of a small, preliminary study of 19 people infected with both HIV—the virus that ...

Naltrexone helps HIV positive individuals reduce heavy alcohol use

August 7, 2018
Extended-release naltrexone—an injection that decreases heavy drinking in the general population when taken in conjunction with counseling—appears to help HIV-positive individuals reduce their number of heavy drinking ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.