Enhancing SIV-specific immunity in vivo by PD-1 blockade

V Velu, K Titanji, B Zhu, S Husain, A Pladevega, L Lai… - Nature, 2009 - nature.com
V Velu, K Titanji, B Zhu, S Husain, A Pladevega, L Lai, TH Vanderford, L Chennareddi…
Nature, 2009nature.com
Chronic immunodeficiency virus infections are characterized by dysfunctional cellular and
humoral antiviral immune responses,,. As such, immune modulatory therapies that enhance
and/or restore the function of virus-specific immunity may protect from disease progression.
Here we investigate the safety and immune restoration potential of blockade of the co-
inhibitory receptor programmed death 1 (PD-1), during chronic simian immunodeficiency
virus (SIV) infection in macaques. We demonstrate that PD-1 blockade using an antibody to …
Abstract
Chronic immunodeficiency virus infections are characterized by dysfunctional cellular and humoral antiviral immune responses,,. As such, immune modulatory therapies that enhance and/or restore the function of virus-specific immunity may protect from disease progression. Here we investigate the safety and immune restoration potential of blockade of the co-inhibitory receptor programmed death 1 (PD-1), during chronic simian immunodeficiency virus (SIV) infection in macaques. We demonstrate that PD-1 blockade using an antibody to PD-1 is well tolerated and results in rapid expansion of virus-specific CD8 T cells with improved functional quality. This enhanced T-cell immunity was seen in the blood and also in the gut, a major reservoir of SIV infection. PD-1 blockade also resulted in proliferation of memory B cells and increases in SIV envelope-specific antibody. These improved immune responses were associated with significant reductions in plasma viral load and also prolonged the survival of SIV-infected macaques. Blockade was effective during the early (week 10) as well as late (∼week 90) phases of chronic infection even under conditions of severe lymphopenia. These results demonstrate enhancement of both cellular and humoral immune responses during a pathogenic immunodeficiency virus infection by blocking a single inhibitory pathway and identify a novel therapeutic approach for control of human immunodeficiency virus infections.
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