# The functional significance of CTL escape

> **NIH NIH R01** · GEORGE WASHINGTON UNIVERSITY · 2021 · $917,023

## Abstract

Project Summary/Abstract
 We have recently performed a vaccine trial using Mamu-B*17+ Indian rhesus macaques, which
demonstrated remarkable control of chronic phase viral replication in five “rapid controller” animals.
Control correlated with the development of increased endpoint titers of vaccine-induced anti-gp140
binding antibodies (Abs) on day of challenge. These Abs did not neutralize the simian
immunodeficiency virus mac239 (SIVmac239) clone. We have rarely seen this type of stringent control of
SIVmac239 replication in more than 130 intrarectally (IR)-challenged macaques with the same dose of this
stock of SIVmac239. In Specific Aim I, we will investigate whether the vaccine-induced Env-binding Abs
in the Mamu-B*17+ “rapid controller” animals either had direct anti-viral effects or facilitated the
development of efficacious T-cell responses. We will address this hypothesis by utilizing two different
approaches involving transfer of serum IgG and monoclonal antibodies (mAbs) from the “rapid
controller” animals to vaccinated and naïve animals.
 We will also investigate the nature of control in Mamu-B*08+ Indian rhesus macaques. More than 50%
of naïve (no vaccine or drug treatment) Mamu-B*08+ macaques become “elite controllers” (ECs) after
infection with SIVmac239. In Specific Aim II, we will determine the genes involved in the control of the
innate immune response that influence the development of elite control in macaques that express
Mamu-B*08.
 It is becoming increasingly apparent that classical vaccine-induced CD8+ T-cells by themselves will
not be sufficient to either prevent or control human immunodeficiency virus (HIV) or SIV infection. Recent
studies have suggested that in conjunction with other effector molecules (Abs, innate immune responses)
CD8+ T-cells can function effectively in the control of HIV/SIV replication in vaccinated individuals. Our
studies plan to elucidate these mechanisms in two cohorts of macaques where unusual control of SIV
replication has been observed.

## Key facts

- **NIH application ID:** 10065481
- **Project number:** 5R01AI052056-20
- **Recipient organization:** GEORGE WASHINGTON UNIVERSITY
- **Principal Investigator:** David I Watkins
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $917,023
- **Award type:** 5
- **Project period:** 2003-04-01 → 2023-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10065481

## Citation

> US National Institutes of Health, RePORTER application 10065481, The functional significance of CTL escape (5R01AI052056-20). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10065481. Licensed CC0.

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