The strategy of Woodruff, the Center for Health Sciences | Feb. 24, 2016
A strategy called "kicking and killing", aimed at activating latent HIV-infected cells so that the virus can be destroyed, came about a long time ago.
Researchers from Yerkes have been looking for a possible way to do so in a model of non-human primates (SIC) and reported their findings at the Conference on Retroviruses and Opportunistic Infections in Boston.
An immune-boosting treatment may force SIV to come out of its hiding places in infected monkeys that have the virus controlled with antiretroviral drugs, scientists report at the National Primate Research Center at the University of Emory in Yerkes. The results were presented Wednesday, February 24 at the Conference on Retroviruses and Opportunistic Infections in Boston by a graduate student named Geetha Mylvaganam. Rama Rao Amara, PhD, Professor of Microbiology and Immunology at Yerkes and the Emory Vaccine Center, led the project. Collaborators involved in the study, such as Rafi Ahmed, PhD, Director of Vaccine Center and an eminent scholar of Emory Georgia, European Alliance of Research and Gordon Freeman, PhD, of the Dana-Farber Cancer Institute. Mylvaganam is part of the graduate program in molecular pathogenesis and immunology at Emory.
With antiretroviral drug control, one can usually keep HIV in chronically infected people, but they can not completely eliminate it. This is because some immune cells harbor the virus latently. One strategy came up called "kicking and killing", aimed at activating these cells, so that the virus can be eliminated from the body.
The Yerkes team tested the effects of blocking Pd 1, a molecule that inhibits the immune response during chronic infections in combination with antiretroviral therapy. Antibodies that block PD-1 have also been tested with some success as immunotherapeutic agents against cancer. The team developed a "primate" anti-PD 1 antibody to reduce the monkey's immune responses to the antibody itself and allow repeated infusions.
With some monkeys infected with SIV, the researchers treated them with anti-PD-1 antibody for 14 days, starting ten days before antiretroviral therapy started. In this situation, animals treated with the anti-PD-1- showed more rapid viral suppression (mean 42 days in the PD-1 group versus 140 days in controls) and a larger number of active antiviral T cells.
In addition, other monkeys infected with SIV were treated with anti-PD-1 antibody (three infusions, one month in each) after antiretroviral therapy had brought viral levels to a very low level. This resulted in transient recurrences of SIV in their blood, not seen in animals used as controls.
The researchers conclude: "These results reveal for the first time the potential for blocking PD-1, both on antiviral restoration of CD8 T cell function, and possibly destabilizing the viral reservoir under HAART. They highlight the potential for blocking PD-1 to work in synergy with other therapeutic agents such as vaccines and latency agents to effectively decrease HIV reservoirs under ART as a means of establishing a functional cure. "
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