# Harnessing IL-10 in cART treated SIV infected macaques to restore immunity and to eradicate HIV

> **NIH NIH R37** · CASE WESTERN RESERVE UNIVERSITY · 2020 · $636,715

## Abstract

While current ART has prevented AIDS and reduced HIV-related morbidities and mortality for the majority of
infected individuals, a therapeutic regimen able to eradicate or functionally cure HIV infection does not exist.
Persistence of HIV in a small pool of latently infected cells remains the major obstacle for HIV eradication
largely because the mechanisms that underlie viral persistence are still unknown. Our group has generated
significant and convincing results in cART treated HIV infected humans and SIV infected rhesus macaques
(RMs) suggesting that Interleukin(IL)-10 plays an important role in the establishment and maintenance of
the HIV reservoir by (i) impeding the early antiviral innate and the HIV/SIV specific adaptive immune response
and (ii) promoting the differentiation of Tfh and Tr1 cells that are major HIV/SIV reservoirs. The importance of
IL-10 in the establishment and maintenance of HIV has prompted Merck to successfully develop a Rhesus
form of an anti-human IL-10 Ab that is currently being tested in clinic; administration of this Ab in a proof of
concept study to SIV infected RMs was safe and well tolerated; it also recapitulated several of the biological
activities of the human Ab as it showed a negative impact on Tfh frequencies which could translate in a smaller
reservoir. In this proposal, we will test the hypothesis that neutralization of IL-10 activity systemically
and in lymphoid tissues will lead to restoration of cellular immune responses, decreased Tfh and Tr1
numbers, and a decay in HIV reservoir. Biomarkers that predict successful clinical interventions involving
anti-IL-10 and leading to HIV eradication are not available. In Aim 1, we will perform an unbiased OMICs
integrated approach to identify cell subsets, soluble effector molecules, metabolites and molecular pathways,
which underlie the modulation of HIV reservoirs by IL-10 in cell subsets isolated from PBMCs and tissues from
cART treated HIV infected subjects. We will identify markers that are associated to low levels of IL-10 and
conversely to lower HIV reservoir in Tfh and Tr1 cells and efficient innate antiviral and cell mediated immunity.
These markers will be used to monitor the impact of the anti-IL-10 intervention that aims at restoring innate
antiviral immunity and cell mediated immunity for HIV eradication. Direct demonstration that IL-10 regulates
HIV persistence will be provided by examining the impact of IL-10 blockade on virus persistence in a large
study of ART-treated, SIV-infected RMs. Preclinical trial of Aim 2 will allow us to determine the restoration of
innate immunity by early IL-10 blockade as this intervention should inhibit the upregulation of NLRX-1, a
molecule we have shown to play a critical role in the early HIV/SIV dissemination and conversely in the
seeding of the HIV/SIV reservoir. Pre-clinical trial of Aim 3 should allow the restoration of the adaptive immune
response by preventing the development of IL-10 producing Tr1 cells;...

## Key facts

- **NIH application ID:** 9979743
- **Project number:** 5R37AI141258-03
- **Recipient organization:** CASE WESTERN RESERVE UNIVERSITY
- **Principal Investigator:** Rafick Pierre Sekaly
- **Activity code:** R37 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $636,715
- **Award type:** 5
- **Project period:** 2018-07-01 → 2020-09-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9979743

## Citation

> US National Institutes of Health, RePORTER application 9979743, Harnessing IL-10 in cART treated SIV infected macaques to restore immunity and to eradicate HIV (5R37AI141258-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9979743. Licensed CC0.

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