# Project 1

> **NIH NIH P01** · UNIVERSITY OF CALIFORNIA AT DAVIS · 2023 · $551,228

## Abstract

ABSTRACT
In order to effectively control HIV after ART is stopped, HIV-specific T cell responses to
therapeutic vaccination must not only be increased in magnitude, but they also must be long-
lived, have the capacity to home to sites of reservoir persistence, have the T cell memory-like
capacity to robustly proliferate and execute effector functions in response to antigen (i.e., they
need to overcome the residual T cell exhaustion that persists in pre-existing HIV-specific T cells
despite viral load suppression with ART), and be refocused to have dominant responses that
target vulnerable epitopes. Due to the limitations of standard T cell assays, and despite
emerging data from clinical trials showing at least partial control of HIV post-vaccination, little is
known about the mechanisms by which HIV therapeutic vaccine regimens transform ineffective
pre-existing HIV-specific T cell immunity into an effective antiviral response. In this Project, we
will leverage our experience performing integrated multi-modal systems immunology analysis
with paired single cell transcriptome and TCR sequencing (scRNA/TCRseq) data and high-
dimensional flow cytometry data. We will perform clonal-level analysis on HIV/SIV therapeutic
vaccine-elicited CD8+ T cells from highly unique and clinically relevant human and macaque
HIV/SIV cohorts in which therapeutic vaccines have exerted a measurable effect on altering
viral load kinetics after treatment interruption to ask: to what extent are current top-candidate
therapeutic vaccine regimens capable of recruiting new and/or pre-existing T cell clones with
optimal memory-like properties (function and differentiation state; Aims 1 and 2), and to what
extent do memory-like features (or other features) of the vaccine-elicited T cell response
correlate with post-treatment control of HIV (Aim 3)? These studies will allow us to characterize
in unprecedented depth the impact of different therapeutic vaccine regimens on critical – and
previously unmeasurable – facets of the quality of the virus-specific T cell response. Our results
will lay the groundwork for us to develop reliable measurements of virus-specific T cell clonal
structure and differentiation state that will inform iterative studies in humans and macaques.

## Key facts

- **NIH application ID:** 10731713
- **Project number:** 1P01AI178375-01
- **Recipient organization:** UNIVERSITY OF CALIFORNIA AT DAVIS
- **Principal Investigator:** DENNIS J. HARTIGAN-O'CONNOR
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $551,228
- **Award type:** 1
- **Project period:** 2023-05-22 → 2028-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10731713

## Citation

> US National Institutes of Health, RePORTER application 10731713, Project 1 (1P01AI178375-01). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10731713. Licensed CC0.

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