Dual antibody treatment suppresses HIV-like virus in monkeys

Protein-structure model showing how the broadly neutralizing antibodies 10-1074 (blue) and 3BNC117 (red) each bind to a different site on the SHIV spike (beige and pink).Gristick et al., Nature Structural & Molecular Biology 2016.

HIV, the virus that causes AIDS, attacks the body’s immune system. This assault leaves people vulnerable to developing other infections and diseases. Although treatments can control HIV infection, HIV persists in the body for a lifetime.

Researchers have isolated many human antibodies that neutralize multiple strains of HIV. Scientists have gained important insights into how these broadly neutralizing antibodies bind to the virus and why they’re effective. However, designing a strategy that allows the human immune system to mount an effective attack against the virus remains a challenge.

A team led by Dr. Malcolm A. Martin at NIH’s National Institute of Allergy and Infectious Diseases (NIAID) and Dr. Michel C. Nussenzweig at Rockefeller University has been exploring therapeutic approaches using broadly neutralizing antibodies. Their latest study, in rhesus macaques, appeared online on March 13, 2017, in Nature.

The researchers inoculated 13 monkeys with SHIV, an HIV-like virus that infects monkeys. Three days afterward, when infection could first be confirmed, the scientists began intravenous infusions of 2 potent, broadly neutralizing HIV antibodies. The antibodies, called 3BNC117 and 10-1074, each bind to a different site on SHIV. The animals received 3 antibody infusions over a 2-week period.

The infusions suppressed SHIV to levels near or below the limit of standard detection methods for as long as 6 months. The virus then rebounded in all but one animal. However, 5 to 22 months later, the immune systems of 6 monkeys regained control of the virus, and the virus remained undetectable for another 5 to 13 months. These monkeys had continuously maintained healthy levels of key immune cells after receiving the antibody infusions.

Four other monkeys that failed to regain complete control of the virus maintained extremely low levels of SHIV in their blood for 2–3 years after infection. Thus, 10 of the 13 monkeys gained lasting benefits from the neutralizing HIV antibodies.

Immune cells called CD8+ T cells help destroy infected cells. To test whether these immune cells played a role in the extended control of SHIV, the scientists depleted CD8+ T cells in the 6 controller monkeys. Without these immune cells, SHIV levels in the monkeys’ blood rose, showing that CD8+ T cells were responsible for controlling SHIV after the antibody infusions.

“What really surprised us was that we could control SHIV for 2 to 3 years without any anti-viral drugs by infusing the antibodies right after the animals became infected,” Martin says.

Studies are now underway to test whether receiving neutralizing antibodies 2 to 6 weeks after infection—timing that more closely resembles how soon an HIV-infected person first seeks medical attention—will still enable monkeys to control SHIV. Clinical trials testing the antibody combination in people are also underway. Researchers are now recruiting HIV-infected and uninfected adults.