This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. 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. We investigated the safety and immune restoration potential of the blockade of co-inhibitory receptor programmed death-1 (PD-1) during chronic SIV infection in macaques. We demonstrated 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. Impressively, blockade was effective during the early (wk10) as well as late (~wk90) 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 HIV/AIDS.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Primate Research Center Grants (P51)
Project #
5P51RR000165-50
Application #
8172452
Study Section
Special Emphasis Panel (ZRR1-CM-8 (01))
Project Start
2010-05-01
Project End
2011-04-30
Budget Start
2010-05-01
Budget End
2011-04-30
Support Year
50
Fiscal Year
2010
Total Cost
$54,827
Indirect Cost
Name
Emory University
Department
Otolaryngology
Type
Schools of Medicine
DUNS #
066469933
City
Atlanta
State
GA
Country
United States
Zip Code
30322
Claw, Katrina G; George, Renee D; MacCoss, Michael J et al. (2018) Quantitative evolutionary proteomics of seminal fluid from primates with different mating systems. BMC Genomics 19:488
Adekambi, Toidi; Ibegbu, Chris C; Cagle, Stephanie et al. (2018) High Frequencies of Caspase-3 Expressing Mycobacterium tuberculosis-Specific CD4+ T Cells Are Associated With Active Tuberculosis. Front Immunol 9:1481
Beck, Goichi; Maehara, Shunsuke; Chang, Phat Ly et al. (2018) A Selective Phosphodiesterase 10A Inhibitor Reduces L-Dopa-Induced Dyskinesias in Parkinsonian Monkeys. Mov Disord 33:805-814
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Mavigner, Maud; Habib, Jakob; Deleage, Claire et al. (2018) Simian Immunodeficiency Virus Persistence in Cellular and Anatomic Reservoirs in Antiretroviral Therapy-Suppressed Infant Rhesus Macaques. J Virol 92:
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