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Novel Strategies for Eliminating HIV

Novel Strategies for Eliminating HIV

Using special antibodies to attack HIV.

More than thirty-five million people in the world today are living with HIV/AIDS. In the last few decades there have been concerted, large-scale efforts worldwide to contain the spread of this pandemic and to help infected people survive the virus and live with it.

At the forefront of anti-HIV therapy stands a class of drugs known as anti-retroviral therapy or ART. These drugs are able to reduce the numbers of virus-infected immune cells in blood circulation but are unable to eliminate it completely. One of the major challenges of HIV research is to find ways to eliminate host cells that are infected but are dormant. Once patients stop taking ART, production of viruses from infected reserves of dormant T-cells resumes and the disease progresses anew.

In two recently published papers, scientists from two different labs have achieved some success in activating the virus in dormant T-cells and simultaneously getting the body’s T-cells to target such reactivated cells.

Antibodies

Antibodies are Y-shaped molecules wherein the short arms of the Y can physically bind to specific proteins. Usually, both arms recognize the same protein. The strategy involves generation of dual-specificity antibodies that can, quite literally, bind HIV-infected and other vigilant T-cells at the same time.

The HIV-1 virus produces a protein known as the Env protein. A specific class of immune cells, known as T-cells, produce a protein known as CD3. This protein is expressed by T-cells that can harbor latent HIV-1 infection as well as by T-cells that are capable of killing the infected T-cells. In this case, these scientists used various DNA-based techniques to produce hybrid antibodies that could recognize the Env protein on one arm and the CD3 protein on the other.

In laboratory systems these dual-spec antibodies were able to get dormant, infected T-cells to reproduce the virus and simultaneously attract other T-cells that could kill the infected cells. In one study the dual-spec antibodies were tested in rhesus macaque monkeys infected with the simian HIV virus. The combination of these novel antibodies and ART was able to reduce the load of viruses in blood to undetectable levels within thirty weeks.

These new results represent a huge breakthrough in the fight against HIV. The next goal is to apply this therapy not just to experimental systems, but to people living with HIV.

References:
Pegu, A., Asokan, M., Wu, L., Wang, K., Hataye, J., Casazza, J., Guo, X., Shi, W., Georgiev, I., Zhou, T., Chen, X., O’Dell, S., Todd, J., Kwong, P., Rao, S., Yang, Z., Koup, R., Mascola, J., & Nabel, G. (2015). Activation and lysis of human CD4 cells latently infected with HIV-1 Nature Communications, 6 DOI: 10.1038/ncomms9447
Sung, J., Pickeral, J., Liu, L., Stanfield-Oakley, S., Lam, C., Garrido, C., Pollara, J., LaBranche, C., Bonsignori, M., Moody, M., Yang, Y., Parks, R., Archin, N., Allard, B., Kirchherr, J., Kuruc, J., Gay, C., Cohen, M., Ochsenbauer, C., Soderberg, K., Liao, H., Montefiori, D., Moore, P., Johnson, S., Koenig, S., Haynes, B., Nordstrom, J., Margolis, D., & Ferrari, G. (2015). Dual-Affinity Re-Targeting proteins direct T cell–mediated cytolysis of latently HIV-infected cells Journal of Clinical Investigation, 125 (11), 4077-4090 DOI: 10.1172/JCI82314

Photo: NIAID / Flickr

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