Newly Discovered Antibody Therapy Leads to Long-term Viral Suppression

Researchers at the Conference on Retroviruses and Opportunistic Infections explained how an antibody against the alpha-4 beta-7 intern receptor sustained long-term viral suppression in monkeys for up to two years after stopping antiretroviral therapy, while also replenishing key immune cells in the gut. 

For those who don't know, alpha-4 beta-7 is an integrin receptor found in the outer envelopes of both HIV and SIV, the virus equivalent to HIV found in monkeys. By blocking alpha-4 beta-7, rather than the virus itself, it is believed to reduce the likelihood of transmission of SIV and HIV.

But what the scientists discovered, nearly by accident, is that the alpha-4 beta-7 molecules on T-cells are receptors for the HIV envelope.

Researchers wound up using a monoclonal antibody against the alpha-4 beta-7 integrin similar to the drug vedolizumab, which is used for treatment of inflammatory bowel disease. Much to their surprise, the drug kept the virus in check.

Our gut's lining contains epithelial cells that have adhesion molecules, which wait to capture cells expressing the appropriate receptors.

The molecule MAdCAM1, which largely lives in the gut, looks for the alpha-4 beta-7 receptor, and thus attracts T-cells carrying that receptor. As newly created virus particles are formed from a host cell, they take a part of that cell’s membrane — and its alpha-4 beta-7 receptors become incorporated into the viral envelope. 

Dr. Christina Guzzo of the US National Institutes of Allergy and Infectious Diseases, and her team, found that virus-associated alpha-4 beta-7 is functionally active, just as it is on the cell surface, reports AIDS Map. After experimentation, it was discovered that only a viruses carrying alpha-4 beta-7 were captured by MAdCAM1 and infected other target cells in the laboratory. 

By incorporating alpha-4 beta-7 into HIV-1 visions, researchers promoted retention of the virus in gut tissues, which are extremely vulnerable during early transmission of HIV. As a result, overall suppression became apparent. 

Because alpha-4 beta-7 exists on both the virus and susceptible cells, the antibody itself captures both and present them to our immune systems to induce long-lasting immune defense. 

“[The antibody therapy might] teach the immune system to recognize HIV in a way it doesn’t recognize it if it just sees HIV alone," Dr. Anthony Fauci of NIAID said. "Our job now is to find out just what the nature of that immune response is."