T Cell Traffic Stop Halts SIV

An antibody used to treat Crohn’s disease controls simian immunodeficiency virus infection in Rhesus macaques by blocking T cell migration to the gut.

By | October 13, 2016

Immuno-PET/CT analysis confirms the preservation of CD4+ cells during a4b7 antibody treatment. SCIENCE, S. BYRAREDDY ET AL. Treatment with an antibody that blocks T cell migration to the gut eliminates detectable viremia in simian immunodeficiency virus (SIV)-infected Rhesus macaques withdrawn from antiretroviral therapy (ART), according to a study published today (October 13) in Science. The effect continued for 18 weeks after the last intravenous antibody infusion.

“With standard retroviral drugs, once you withdraw them, the virus comes back. And here is a case where the virus isn’t coming back,” said viral immunologist David Montefiori of Duke University in North Carolina who was not involved in the work.

The antibody binds a molecule on T cells called α4β7, which directs T cells to gut lymphoid tissues “like a zip code on the cells,” explained study coauthor Aftab Ansari, a pathologist at Emory University in Atlanta. Because the gut is a major site of viral replication and CD4+ T-cell infection in SIV and HIV, Ansari said, “if these cells are trafficking into the gut, they are basically adding fuel to fire.”

Ansari and colleagues at the National Institute of Allergy and Infectious Diseases (NIAID) previously showed the antibody could prevent vaginal transmission of SIV in 50 percent of infected macaques and minimize viral replication and CD4+ T cell loss in gut tissues.

For the present study, the team administered the antibody and ART to eight macaques with established SIV infections. The researchers then discontinued ART, causing viral replication to spike, and administered antibody infusions for 14 more weeks before halting all treatment. In the following 18 weeks, viral DNA dropped to undetectable levels in blood and gut tissues in animals that received the α4β7 antibody.

“All of the animals have remarkable control of viremia,” said Montefiori.

The treatment group also maintained normal numbers of CD4+ T cells. Animals that received a control antibody all experienced high viral loads and low CD4+ T cell numbers, and eventually died.

According to Ansari, after two years with no further treatment, the experimental group animals are still alive and being examined as part of ongoing studies to understand the immunological mechanisms behind the prolonged protection.

A humanized version of the same antibody, manufactured by Takeda Pharmaceuticals, is already approved by the US Food and Drug Administration for the treatment Crohn’s disease and ulcerative colitis. The NIAID has initiated a phase 1 trial to test the drug’s safety in HIV-positive people.

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