# B and T Cell Biology of Protection from and Eradication of SIV/SHIV Infection - Administrative Supplement

> **NIH NIH UM1** · EMORY UNIVERSITY · 2021 · $6,714,942

## Abstract

ABSTRACT
The Emory Consortium for Innovative AIDS Research in Nonhuman Primates aims to understand the B and T
cell biology of protection from and eradication of SIV/SHIV infection. The consortium brings together highly
collaborative, and productive investigators in a range of HIV vaccine and cure disciplines to address the
overarching hypothesis that a successful prophylactic HIV vaccine will require a strong and sustained systemic
and mucosal immune response, comprised of functionally targeted antibody and tissue resident CD8 T cell
immunity, in concert with a modulated HIV-specific CD4 T cell response that maintains low numbers of HIV
targets in mucosal tissue, while providing adequate help for a strong adaptive response. Moreover, we postulate
that in the context of novel active latency reversing agents, immunomodulatory approaches to directly kill
reactivated cells through antiviral antibodies and increased sensitivity to apoptosis will reduce viral reservoirs
and thus maintain suppression of virus replication following cessation of anti-retroviral drugs. The approaches
summarized in FOCUS 1 of the aims below will utilize state of the art adjuvants coupled with native trimeric Env
immunogens to induce and mechanistically dissect strong durable humoral responses. In addition, we aim to
fully characterize and harness a novel population of tissue resident CD8 T cells to effectively synergize with the
humoral immune response in providing protection from heterologous SHIV challenge. In FOCUS 2 we will utilize
novel latency reversing agents and CD8+ T cell depletion to define an optimal reactivation program, and then
will combine these with the antiviral monoclonal antibodies and inhibitors of BCL-2 to explore the potential of this
combination to yield a sustained suppression of virus replication following cART withdrawal. These experimental
approaches will be supported by 5 state of the art Scientific Research Support Cores in order to fully characterize
the magnitude, function, specificity and repertoire of the humoral response. Single cell analytics and
transcriptomics will also support characterization of innate and adaptive signals at the cellular level. This
supplement application for this comprehensive program has two specific aims. In Aim 1 (FOCUS 1), we will
test the synergy between functional antibody response and tissue resident T cells in providing long-term
protection against a heterologous tier-2 intravaginal clade C SHIV challenge. In Aim 2 (FOCUS 2), we will test if
a combination of a cocktail of anti-SIV monoclonal antibodies and a compound, venetoclax, shown in vitro to
sensitize reservoir cells to apoptosis help to reduce viral reservoirs in the setting of potent reversal of viral latency.
Results from these studies will have important implications for the development of effective preventive vaccines
and cure strategies for HIV.

## Key facts

- **NIH application ID:** 10294511
- **Project number:** 3UM1AI124436-05S1
- **Recipient organization:** EMORY UNIVERSITY
- **Principal Investigator:** Rama Rao Amara
- **Activity code:** UM1 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $6,714,942
- **Award type:** 3
- **Project period:** 2016-06-01 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10294511

## Citation

> US National Institutes of Health, RePORTER application 10294511, B and T Cell Biology of Protection from and Eradication of SIV/SHIV Infection - Administrative Supplement (3UM1AI124436-05S1). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10294511. Licensed CC0.

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