Update on SIV remission studies

Tab Ansari’s research at Emory/Yerkes on how an antibody treatment can push monkeys infected with SIV into remission was published in Science last year. At that time, Ansari told Lab Land about follow-up experiments to probe which immune cells are needed for this effect, which surprised many HIV/AIDS experts.

Ansari’s partner on the project, NIAID director Anthony Fauci, described the follow-up work in July at the International AIDS Society Conference in Paris. We thank Treatment Action Group’s Richard Jefferys for taking notes and posting a summary:

The approach that the researchers took was to deplete different types of immune cells in the animals controlling SIV viral load, then assess whether this led to an increase in viral replication. The experiments compared:

*Antibodies to the CD8 receptor alpha chain, which deplete CD8 T cells, natural killer T cells (NKTs) and natural killer (NK) cells

*Antibodies to the CD8 receptor beta chain, which deplete CD8 T cells

*Antibodies to CD20, which deplete B cells

According to Fauci’s slides, which are available online, there was a transient rebound in viral load with the CD8 alpha antibody and to a small degree with the CD8 beta. This suggests NKTs and NK cells are making a contribution to the observed control of SIV replication, but a role for CD8 T cells cannot be ruled out.

For comparison, a study from Guido Silvestri and colleagues at Yerkes published in 2016 found that treating SIV-infected monkeys with anti-CD8 antibodies, without stopping antiretroviral drugs, resulted in a rebound in virus levels. [They used ultrasensitive assays to detect the rebound.] However, the Yerkes team only used antibodies to the CD8 receptor alpha chain.

Also in Paris, Jim Arthos of NIAID presented an imaging study on the monkeys that had undergone SIV remission, performed with Emory and Georgia Tech researchers. Several other Emory and Yerkes abstracts were presented, and we aim to cover them more extensively later.

This past spring, NIAID researchers reported separate work on how the antibody suppresses HIV and SIV, which was published in May in Science Immunology. Bottom line: the antibody target (integrin a4b7, an adhesion molecule prominent in the intestine) is on the virus in addition to immune cells, but antibody treatment also appears to induce an “unusually effective immune response” that continues to restrain the virus for long time periods.

At Yerkes, Mirko Paiardini is collaborating with the first author of the SIV remission Science paper, Siddappa Byrareddy, who is now at University of Nebraska. They are combining the anti-integrin antibody with IL21 treatment, which Paiardini’s group had found enhances intestinal immune reconstitution after the acute phase of SIV infection.

Additional links:

Ongoing NIH clinical trial of vedolizumab with HIV infection

Similar trial planned in Canada

 

 

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Posted on by Quinn Eastman in Immunology Leave a comment

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Quinn Eastman

Science Writer, Research Communications qeastma@emory.edu 404-727-7829 Office

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