Publication Date:
2008-12-17
Description:
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 ( approximately 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.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2753387/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2753387/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Velu, Vijayakumar -- Titanji, Kehmia -- Zhu, Baogong -- Husain, Sajid -- Pladevega, Annette -- Lai, Lilin -- Vanderford, Thomas H -- Chennareddi, Lakshmi -- Silvestri, Guido -- Freeman, Gordon J -- Ahmed, Rafi -- Amara, Rama Rao -- P30 AI050409/AI/NIAID NIH HHS/ -- P51 RR00165/RR/NCRR NIH HHS/ -- R01 AI057029/AI/NIAID NIH HHS/ -- R01 AI057029-01/AI/NIAID NIH HHS/ -- R01 AI057029-02/AI/NIAID NIH HHS/ -- R01 AI057029-03/AI/NIAID NIH HHS/ -- R01 AI057029-04/AI/NIAID NIH HHS/ -- R01 AI057029-05/AI/NIAID NIH HHS/ -- R01 AI071852/AI/NIAID NIH HHS/ -- R01 AI074417/AI/NIAID NIH HHS/ -- R01 AI074417-01A1/AI/NIAID NIH HHS/ -- R01 AI074417-02/AI/NIAID NIH HHS/ -- R24 RR16038/RR/NCRR NIH HHS/ -- England -- Nature. 2009 Mar 12;458(7235):206-10. doi: 10.1038/nature07662. Epub 2008 Dec 10.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Emory Vaccine Center, Emory University School of Medicine, Atlanta, Georgia 30322, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19078956" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
Antibodies, Monoclonal/administration & dosage/*metabolism/pharmacology
;
Antibodies, Viral/blood
;
Antibody Formation/drug effects/immunology
;
Apoptosis Regulatory Proteins/*metabolism
;
CD8-Positive T-Lymphocytes
;
Gene Products, gag/blood
;
Immunity, Innate/*drug effects
;
Intestines/drug effects/immunology
;
Macaca mulatta
;
Molecular Sequence Data
;
Simian Acquired Immunodeficiency Syndrome/*immunology
;
Simian Immunodeficiency Virus/*immunology
;
Survival Analysis
;
Viremia/immunology
Print ISSN:
0028-0836
Electronic ISSN:
1476-4687
Topics:
Biology
,
Chemistry and Pharmacology
,
Medicine
,
Natural Sciences in General
,
Physics
