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

> **NIH NIH UM1** · EMORY UNIVERSITY · 2024 · $5,678,510

## Abstract

ABSTRACT
The Emory Consortium for Innovative HIV/AIDS Vaccine and Cure Research in Nonhuman Primates aims to
define the mechanisms of the B and T Cell Biology of Protection from and Eradication of SHIV Infection. The
consortium brings together an interdisciplinary mix of highly collaborative, and productive investigators in a range
of HIV vaccine and cure disciplines to address the overarching hypothesis that the success of the prophylactic
HIV vaccine we have developed during the current program is due to a combination of a strong and sustained
systemic and mucosal immune response. This is comprised of multi-functional antibody and tissue resident CD8
T cell immunity, which upon encountering cognate antigen responds through conventional cytolytic mechanisms
and through modulation of the mucosal environment, such that responding HIV-specific CD4+ T cell are resistant
to infection. Moreover, we postulate that such a potent and balanced vaccine response will, in the context of
active latency reversing agents, reduce viral reservoirs and thus maintain suppression of virus replication
following cessation of highly active antiretroviral therapy.
The approaches in FOCUS 1, aimed at understanding the mechanisms of vaccine protection, will utilize state of
the art techniques and analyses to fully characterize and harness a novel population of tissue resident CD8 T
cells induced by our Heterologous Viral Vector vaccine (HVV vaccine) encoding Gag as an immunogen to
effectively synergize with the humoral immune response induced by our HIV envelope trimer vaccine (Protein
vaccine) co-delivered with novel adjuvants to provide long-term protection against heterologous SHIV challenge
even in the absence of strong neutralizing antibody response. In the later years we will use this novel,
mechanistic information to optimize the vaccine and move it closer to clinical studies. In FOCUS 2 we will pursue,
in SHIV-infected ART-treated macaques, the “shock and kill” approach to induce virus expression from latently
infected cells using latency reversal agents (LRAs) following therapeutic vaccination aimed at boosting virus-
specific immune responses able to clear CD4 T cells in which virus production has been reactivated. First, will
determine how the HVV+Protein vaccine behaves in ART suppressed macaques and then study its ability to
deplete the reservoir in the context of active LRAs and its impact on control of viral rebound.
These experimental approaches will be supported by an effective Operations and Management Support
component and three state of the art Centralized Research Resources to fully characterize the magnitude,
function, specificity and repertoire of the humoral response. Single cell analysis and transcriptomics will also
support characterization of innate and adaptive signals at the cellular level.

## Key facts

- **NIH application ID:** 10878698
- **Project number:** 5UM1AI169662-03
- **Recipient organization:** EMORY UNIVERSITY
- **Principal Investigator:** Rama Rao Amara
- **Activity code:** UM1 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $5,678,510
- **Award type:** 5
- **Project period:** 2022-06-01 → 2027-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10878698

## Citation

> US National Institutes of Health, RePORTER application 10878698, B and T Cell Biology of Protection from and Eradication of SIV/SHIV Infection (5UM1AI169662-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10878698. Licensed CC0.

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