Neutralizing antibodies: an early treatment for HIV

Animal model studies have yielded promising results

Neutralizing antibodies could be suitable for early treatments and to maintain small reservoirs of defense cells’ retrovirus genes. Malcolm Martin from the National Institutes of Health presented current animal experiments looking into this therapeutic approach at the 25th CROI on March 5th, 2018, in Boston.

Neutralizing antibodies were found in patients’ blood samples (defined as elite neutralizers). In these antibodies, viral replication was inhibited at the beginning of the infection even without medication. These antibodies are very active and have a broad spectrum, with about twenty of these antibodies available in monoclonal form. They were researched with animal models in prevention and therapy studies and have shown a promising effect on humans so far. These broadly neutralizing antibodies attack six regions of the HIV-1 virus’ transmembrane envelope.

National Institutes of Health (NIH) researchers treated asymptomatic macaques that were chronically infected with the Simian Human Immunodeficiency Virus (SHIV) with a combination of the 3BNC117 and 10-1074 antibodies, resulting in two animals suffering from viral plasma suppression over several weeks. In a second dose, one animal developed resistance and the second one showed continued suppression of viremia.

In the following approach, the NIH researchers investigated the antibodies’ effect in acute infections. They inoculated SHIV to 13 macaques intrarectally or intravenously. After inoculation, they injected the 3BNC117 and 10-1074 antibodies into the animals on days 3,10 and 17. Each of these antibodies binds to different parts of the SHIV, neutralizes the virus, and facilitates clearance throughout the immune system.

As a result of antibody delivery, SHIV levels dropped below the detection limit of standard assays for up to 6 months. However, as soon as the antibodies were completely eliminated, virus replication took place again, except in one animal. Yet in 6 macaques, the so-called Elite Controllers (also known as LTNPs), the virus concentration dropped below the detection limit for another 5 to 13 months after 5 to 22 months without further treatment. Arguably, antibodies treatment strengthened the ability of CD8 cells to inhibit viral replication. When antibodies were given to the monkeys for CD8 cells elimination, virus replication was resumed exponentially. CD8-T cells are believed to play an important role in the control of viremia.

A control group infected with SHIV received combined antiretroviral therapy (cART) for 15 weeks. During the treatment, the viral concentration also decreased but increased sharply as soon as the therapy ended. The cART was therefore unable to induce an Elite Controller status.

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