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Dual blockade of IL-10 and PD-1 leads to control of SIV viral rebound following analytical treatment interruption

Journal Article · · Nature Immunology
 [1];  [2];  [3];  [4];  [4];  [4];  [4];  [5];  [6];  [2];  [2];  [2];  [2];  [2];  [7];  [8];  [9];  [9];  [9];  [10] more »;  [11];  [12];  [13];  [13];  [14];  [9];  [10];  [10];  [14];  [1] « less
  1. Emory Univ., Atlanta, GA (United States). School of Medicine and Winship Cancer Institute; Emory Vaccine Center, Atlanta, GA (United States)
  2. Emory Univ., Atlanta, GA (United States). National Primate Research Center
  3. Emory Univ., Atlanta, GA (United States). School of Medicine; Centre de recherche Azrieli du CHU Sainte-Justine, Montreal, QC (Canada); Univ. of Montreal, QC (Canada)
  4. Emory Univ., Atlanta, GA (United States). School of Medicine
  5. Emory Univ., Atlanta, GA (United States). School of Medicine; Instituto Nacional de Enfermedades Respiratorias, Mexico City (Mexico)
  6. RPM Bioinfo Solutions, Blainville, QC (Canada)
  7. Becton Dickinson, San Jose, CA (United States)
  8. Frederick National Lab. for Cancer Research, Frederick, MD (United States)
  9. Merck & Co., Inc., South San Francisco, CA (United States)
  10. Merck & Co., Inc., Rahway, NJ (United States)
  11. Merck & Co., Inc., Boston, MA (United States)
  12. Los Alamos National Laboratory (LANL), Los Alamos, NM (United States)
  13. Oregon Health & Science Univ., Beaverton, OR (United States)
  14. Emory Univ., Atlanta, GA (United States). School of Medicine and National Primate Research Center
+ Show Author Affiliations
Human immunodeficiency virus (HIV) persistence during antiretroviral therapy (ART) is associated with heightened plasma interleukin-10 (IL-10) levels and PD-1 expression. We hypothesized that IL-10 and PD-1 blockade would lead to control of viral rebound following analytical treatment interruption (ATI). Twenty-eight ART-treated, simian immunodeficiency virus (SIV)mac239-infected rhesus macaques (RMs) were treated with anti-IL-10, anti-IL-10 plus anti-PD-1 (combo) or vehicle. ART was interrupted 12 weeks after introduction of immunotherapy. Durable control of viral rebound was observed in nine out of ten combo-treated RMs for >24 weeks post-ATI. Induction of inflammatory cytokines, proliferation of effector CD8+ T cells in lymph nodes and reduced expression of BCL-2 in CD4+ T cells pre-ATI predicted control of viral rebound. Twenty-four weeks post-ATI, lower viral load was associated with higher frequencies of memory T cells expressing TCF-1 and of SIV-specific CD4+ and CD8+ T cells in blood and lymph nodes of combo-treated RMs. These results map a path to achieve long-lasting control of HIV and/or SIV following discontinuation of ART.
Research Organization:
Los Alamos National Laboratory (LANL), Los Alamos, NM (United States)
Sponsoring Organization:
National Institutes of Health (NIH); USDOE
Grant/Contract Number:
89233218CNA000001
OSTI ID:
2472582
Report Number(s):
LA-UR--24-30713
Journal Information:
Nature Immunology, Journal Name: Nature Immunology Journal Issue: 10 Vol. 25; ISSN 1529-2908
Publisher:
Nature Research, Springer NatureCopyright Statement
Country of Publication:
United States
Language:
English

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