April 20, 2015

HIV Immunotherapy Promising in First Human Study

At a Glance

  • A single infusion of an experimental antibody significantly reduced HIV levels in infected people for as long as 28 days.
  • This and similar antibodies might help to combat a wide range of HIV strains.
HIV-infected cells. HIV-infected immune cells.Comstock/Stockbyte/Thinkstock

HIV, the virus that causes AIDS, attacks and destroys immune cells. Current treatment with antiretroviral therapy helps to prevent the virus from multiplying. But despite advances in treatment, scientists haven’t yet designed a vaccine that protects people from HIV.

Researchers have discovered many human antibodies that can neutralize multiple strains of HIV. They’ve gained important insights into how these broadly neutralizing antibodies bind to the virus and why they're effective. However, it’s been a challenge to design a vaccine that prompts the human immune system to generate such antibodies and mount an effective attack against the virus. 

A team led by Dr. Michel C. Nussenzweig of the Howard Hughes Medical Institute at Rockefeller University has been exploring a different approach. In previous work, they isolated broadly neutralizing antibodies from people and produced them in the lab. These so-called monoclonal antibodies could prevent or treat infection with HIV or its monkey equivalent in mice and macaques.

In the current study, the researchers evaluated one of these promising monoclonal anti-HIV antibodies in people. The small phase 1 clinical trial included 29 volunteers — 17 HIV-infected and 12 uninfected. The study was supported by the Bill and Melinda Gates Foundation, NIH’s National Institute of Allergy and Infectious Diseases (NIAID), and others. Results appeared online on April 8, 2015, in Nature.

The participants received a single intravenous dose (of 1, 3, 10, or 30 milligrams per kilogram of body weight) of the experimental antibody called 3BNC117. The antibody was well-tolerated by all participants. Among those infected with HIV, the 2 lower doses caused small and transient changes in blood HIV levels. The 8 participants who received the highest dose, however, had significant and rapid decreases in HIV. The virus’s resistance to the antibody was variable. In some people, HIV remained sensitive to 3BNC117 for 28 days.

“What’s special about these antibodies is that they have activity against over 80% of HIV strains and they are extremely potent,” says study coauthor Dr. Marina Caskey.

“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,” adds coauthor Dr. Florian Klein.

This study suggests that 3BNC117 is safe in people and could help to control HIV. Future studies will continue to explore the use of this and other broadly neutralizing antibodies in HIV prevention and treatment.

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Reference: Viraemia suppressed in HIV-1-infected humans by broadly neutralizing antibody 3BNC117. Caskey M, Klein F, Lorenzi JC, Seaman MS, West AP Jr, Buckley N, Kremer G, Nogueira L, Braunschweig M, Scheid JF, Horwitz JA, Shimeliovich I, Ben-Avraham S, Witmer-Pack M, Platten M, Lehmann C, Burke LA, Hawthorne T, Gorelick RJ, Walker BD, Keler T, Gulick RM, Fätkenheuer G, Schlesinger SJ, Nussenzweig MC. Nature. 2015 Apr 8. doi: 10.1038/nature14411. [Epub ahead of print]. PMID: 25855300.

Funding: NIH’s National Institute of Allergy and Infectious Diseases (NIAID), National Center for Advancing Translational Sciences (NCATS), and National Cancer Institute (NCI); Howard Hughes Medical Institute; Bill and Melinda Gates Foundation; Robertson Foundation; German Center for Infection Research; Mark and Lisa Schwartz Foundation; and CNPq “Ciencia sem Fronteiras” Brazil.