Innate Immune Activation by cGMP-AMP Nanoparticles Leads to Potent and Long-Acting Antiretroviral Response against HIV-1

The Journal of Immunology : Official Journal of the American Association of Immunologists
Chukwuemika ArohNan Yan

Abstract

HIV-1 evades immune detection by the cGAS-STING cytosolic DNA-sensing pathway during acute infection. STING is a critical mediator of type I IFN production, and STING agonists such as cGMP-AMP (cGAMP) and other cyclic dinucleotides elicit potent immune and antitumor response. In this article, we show that administration of cGAMP, delivered by an ultra-pH-sensitive nanoparticle (NP; PC7A), in human PBMCs induces potent and long-acting antiretroviral response against several laboratory-adapted and clinical HIV-1 isolates. cGAMP-PC7A NP requires endocytosis for intracellular delivery and immune signaling activation. cGAMP-PC7A NP-induced protection is mediated through type I IFN signaling and requires monocytes in PBMCs. cGAMP-PC7A NPs also inhibit HIV-1 replication in HIV+ patient PBMCs after ex vivo reactivation. Because pattern recognition receptor agonists continue to show more clinical benefits than the traditional IFN therapy, our data present important evidence for potentially developing cGAMP or other STING agonists as a new class of immune-stimulating long-acting antiretroviral agents.

References

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Citations

Mar 14, 2019·Immunologic Research·Feng SunWenxian Guan
Dec 4, 2019·Medicinal Research Reviews·Jun-Jun WuYan-Mei Li
Aug 23, 2020·Vaccines·Himanshu GogoiLei Jin
Dec 28, 2018·Journal of the Pediatric Infectious Diseases Society·Regina K Rowe, Michelle A Gill
Jan 24, 2020·Cells·Xin YinSumit K Chanda
May 20, 2020·Frontiers in Immunology·Allan BowenRohan Fernandes
Sep 28, 2018·Journal of Controlled Release : Official Journal of the Controlled Release Society·Naihan ChenEric M Bachelder
Dec 2, 2020·Seminars in Immunology·Derek T O'HaganGiuseppe Lofano
Apr 7, 2021·The Journal of Immunology : Official Journal of the American Association of Immunologists·Brandon M JohnsonJenny P-Y Ting
Aug 7, 2021·Molecular Aspects of Medicine·Jiarong ZhouLiangfang Zhang
May 8, 2019·ACS Infectious Diseases·Xiaohui ZhangJinhong Chang
Nov 30, 2018·ACS Nano·Santiswarup SinghaPere Santamaria
Sep 23, 2021·Expert Review of Vaccines·Amrita Das, Nahid Ali

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