Argos Therapeutics Publishes Research on the Immunosuppressive Properties of HIV
Manuscript Published in PLoS One Relevant to Development and Evaluation of HIV Immunotherapies-
Durham, NC– June 10, 2009 — Argos Therapeutics today announced the publication of an article related to its Arcelis™ HIV immunotherapy program in the peer-reviewed online journal PLoS ONE. The publication details research on the progression of HIV infection, virulence factors, the immunosuppressive properties of HIV, and how this research may influence the development of HIV immunotherapies.
The manuscript, titled "The Immunosuppressive Properties of the HIV Vpr protein are Linked to a Single Highly Conserved Residue, R90," details the study of IL-12 suppression by the HIV viral protein R (Vpr) in monocyte-derived dendritic cells (DC). IL-12 is a critical cytokine, required for effective immune responses, that is secreted by macrophages, monocytes and dendritic cells, and is suppressed by Vpr, implicating Vpr as an important virulence factor in HIV infection. Researchers hypothesized that the Vpr protein may be required to establish productive HIV infection, because it disables antigen presenting cells of the first infected mucosal tissues.
Analysis revealed that some previously reported C terminal Vpr mutations do not alleviate the block of IL-12 secretion; however, a novel single conservative amino acid substitution, R90K, completely reverses the suppression. Further analysis demonstrated that R90 may not directly regulate the IL-12 pathway, but instead alleviates the suppressive effect through lowering Vpr intracellular levels. As a result, this study supports Vpr as an HIV virulence factor during HIV infection, and for the first time, provides a link between evolutionary conservation of Vpr and its ability to suppress IL-12 secretion by DCs.
Charles Nicolette, Ph.D., Chief Scientific Officer and Vice President of Research and Development of Argos Therapeutics, said: "Our research suggests a natural selection for sequences that suppress IL-12 secretion by dendritic cells and against mutations that relieve this suppression. Dendritic cells activated in the presence of Vpr are defective in their production of IL-12, which contributes to the progression of HIV infection. Argos’ research into the immunobiology of HIV is providing important information to support those developing and evaluating HIV immunotherapies, including our own based on our Arcelis personalized immunotherapy platform."
The manuscript was authored by: Irina Tcherepanova, Aijing Starr, Melissa Adams, Brad Lackford, David Calderhead, Don Healey, Mohamed-Rachid Boulassel, Jean-Pierre Routy and Charles Nicolette.
The development of Argos’ Arcelis HIV immunotherapy program is part of the Company’s broad collaboration with Kyowa Hakko Kirin Co., Ltd.
About Argos Therapeutics, Inc.
Argos is an immunotherapy company developing new treatments for cancer, infectious and autoimmune diseases, and transplantation rejection. The Company has generated multiple platform technologies and a diverse pipeline of products based on its expertise in the biology of dendritic cells — the master switch that turns the immune system on or off. www.argostherapeutics.com.