Combination anti-PD-1 and antiretroviral therapy provides therapeutic benefit against SIV

JCI Insight
Geetha H MylvaganamRama R Amara

Abstract

Therapeutic strategies that augment antiviral immunity and reduce the viral reservoir are critical to achieving durable remission of HIV. The coinhibitory receptor programmed death-1 (PD-1) regulates CD8+ T cell dysfunction during chronic HIV and SIV infections. We previously demonstrated that in vivo blockade of PD-1 during chronic SIV infection improves the function of antiviral CD8+ T cells and B cells. Here, we tested the immunological and virological effects of PD-1 blockade combined with antiretroviral therapy (ART) in rhesus macaques. Administration of anti-PD-1 antibody 10 days prior to ART initiation rapidly enhanced antiviral CD8+ T cell function and diminished IFN-stimulated genes. This resulted in faster viral suppression in plasma and better Th17 cell reconstitution in the rectal mucosa following ART initiation. PD-1 blockade during ART resulted in lower levels of cell-associated replication-competent virus. Following ART interruption, PD-1 antibody-treated animals showed markedly higher expansion of proliferating CXCR5+perforin+granzyme B+ effector CD8+ T cells and lower regulatory T cells that resulted in better control of viremia. Our results show that PD-1 blockade can be administered safely with ART to augment...Continue Reading

References

Jul 5, 2006·The American Journal of Surgical Pathology·David M DorfmanGordon J Freeman
Aug 19, 2006·Nature Medicine·Lydie TrautmannRafick-Pierre Sekaly
Dec 17, 2008·Nature·Vijayakumar VeluRama Rao Amara
Jun 23, 2009·Nature Medicine·Nicolas ChomontRafick-Pierre Sékaly
Dec 5, 2009·The Journal of Clinical Investigation·Béatrice JacquelinMichaela C Müller-Trutwin
Dec 5, 2009·The Journal of Clinical Investigation·Steven E BosingerDavid J Kelvin
Jan 19, 2011·Current Opinion in HIV and AIDS·Jonathan K L Chan, Warner C Greene
Jan 26, 2011·Cytometry. Part a : the Journal of the International Society for Analytical Cytology·Mario RoedererMartha C Nason
Apr 24, 2012·The Journal of Clinical Investigation·Ravi Dyavar ShettyRama Rao Amara
Aug 29, 2012·Cancer Immunology, Immunotherapy : CII·Masayasu NaitoGordon J Freeman
Dec 21, 2012·The Journal of Experimental Medicine·Matthieu PerreauGiuseppe Pantaleo
Sep 24, 2014·The Journal of Immunology : Official Journal of the American Association of Immunologists·Geetha H MylvaganamRama Rao Amara
Nov 18, 2014·The New England Journal of Medicine·Caroline RobertPaolo A Ascierto
Jun 28, 2015·The Journal of Immunology : Official Journal of the American Association of Immunologists·Smita S IyerRama Rao Amara
Nov 10, 2015·The Journal of Clinical Investigation·Luca MicciMirko Paiardini
Jul 16, 2016·PLoS Pathogens·Rémi FromentinNicolas Chomont

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Citations

Jan 10, 2019·The Journal of Infectious Diseases·Amar Singh, Sujata Prasad
Dec 27, 2018·Current Opinion in HIV and AIDS·Timothy N Hoang, Mirko Paiardini
Dec 29, 2019·Immunological Reviews·Craig FenwickGiuseppe Pantaleo
Nov 7, 2019·Journal of Virology·Lisa J HendersonAvindra Nath
Apr 19, 2020·APMIS : Acta Pathologica, Microbiologica, Et Immunologica Scandinavica·Steffen Leth, Søren Jensen-Fangel
May 21, 2020·The Journal of Infectious Diseases·Bruktawit A GoshuMarta Catalfamo
Jan 18, 2019·PLoS Pathogens·Colin G GraydonKeith R Fowke
Sep 26, 2019·Frontiers in Immunology·Geetha MylvaganamBruce D Walker
May 28, 2020·Frontiers in Cellular and Infection Microbiology·Shokichi Takahama, Takuya Yamamoto
Dec 21, 2018·Frontiers in Immunology·Cordelia ManickamR Keith Reeves
Mar 14, 2019·Frontiers in Immunology·Joanna A WarrenNilu Goonetilleke
Jul 3, 2019·Frontiers in Cellular and Infection Microbiology·Günther Schönrich, Martin J Raftery
Jul 6, 2019·Viral Immunology·Federico Perdomo-CelisMaría T Rugeles
Aug 27, 2019·Frontiers in Immunology·Federico Perdomo-CelisMaria T Rugeles
Jul 31, 2020·Vaccines·Nabila SeddikiVéronique Godot
Jun 9, 2020·Asia-Pacific Journal of Clinical Oncology·Ling LuoTaisheng Li
Jul 1, 2020·Frontiers in Immunology·Janne Tegder MartinsenOle Schmeltz Søgaard
Feb 14, 2020·Nature Reviews. Immunology·David R CollinsBruce D Walker
Jul 28, 2020·Frontiers in Immunology·Selena ViganoAlexandre Harari
Jan 17, 2021·Science Immunology·Keith D KauffmanDaniel L Barber
Sep 9, 2019·Trends in Molecular Medicine·Michael S AbersDimitrios P Kontoyiannis
Mar 19, 2021·Phytotherapy Research : PTR·Syed Afroz AliAshok Kumar Datusalia
Mar 8, 2021·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·Thomas A RasmussenSharon R Lewin
Sep 29, 2020·Seminars in Immunology·Adam R WardR Brad Jones
May 12, 2021·Seminars in Immunology·Anna Kula-PacurarCarine Van Lint
Dec 24, 2021·Nature Reviews. Drug Discovery·Alan J KormanNils Lonberg

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Datasets Mentioned

BETA
GSE111435

Methods Mentioned

BETA
biopsies
RNA-Seq
flow cytometry
PMA
PCR

Software Mentioned

htseq
GraphPad
FlowJo
count
GSEA
STAR
Prism
SPICE
DESeq2

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