# A participant-derived xenograft mouse model to study T-cell-mediated viral control and mRNA vaccine strategies

> **NIH NIH R21** · WEILL MEDICAL COLL OF CORNELL UNIV · 2022 · $254,250

## Abstract

PROJECT SUMMARY/ABSTRACT
Although modern therapies have dramatically improved the outlooks for people living with HIV they are unable
to cure infection, leaving these individuals burdened by a lifelong commitment to antiretroviral (ARV) medication.
For any given individual, maintaining lifelong adherence to medication can present substantial challenges.
Moreover, many people do not have access to these expensive medications - in particular those living in
resource-limited settings. Furthermore, efforts to end the HIV epidemic have suffered from the lack of effective
preventative or therapeutic vaccines – biomedical tools which have played critical roles in the elimination of other
epidemics, such as smallpox. Recent years have seen important advances in harnessing the antibody arm of
the immune system towards these aims, though substantial challenges still exist. The T-cell arm of the immune
system, which specializes in the recognition and elimination of virus infected cells, holds great promise to
contribute to these efforts, but has lagged behind in development. This can be attributed – in part – to substantial
limitations in the suitability of currently available pre-clinical animal models for the study of T-cell responses. For
example, the property of major histocompatibility (MHC) restriction means that the ways in which the virus-
infected cells of a rhesus macaque will recognize a virus-infected cell differ from the way they would be
recognized by a given human. The current proposal aims to build upon compelling preliminary results, in which
we have observed that a relatively simple, but powerful, modification of a humanized mouse model solves many
of the key issues that have limited utility to date. Namely, we present a mouse model that can be stably engrafted
with immune cells (PBMC) from HIV-infected or uninfected adults, without inducing graft versus host disease
(GvHD). The use of adult cells both avoids the need for fetal tissue. In this project, we will test whether HIV-
specific T-cell responses arise naturally in this mouse model, and whether these play a role in suppressing viral
replication. We will then test whether we are able to induce HIV-specific T-cell responses in uninfected animals
using an mRNA vaccine technology, similar to that employed against COVID-19. Finally, we will test whether
vaccine-induced responses can control viral replication. If successful, this will result in a novel small animal
model in which we can rapidly test and optimize HIV vaccination strategies using a mRNA platform. We believe
that this will facilitate the translation of optimal approaches to clinical trials.

## Key facts

- **NIH application ID:** 10483703
- **Project number:** 1R21AI170246-01
- **Recipient organization:** WEILL MEDICAL COLL OF CORNELL UNIV
- **Principal Investigator:** R. Brad Jones
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $254,250
- **Award type:** 1
- **Project period:** 2022-08-12 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10483703

## Citation

> US National Institutes of Health, RePORTER application 10483703, A participant-derived xenograft mouse model to study T-cell-mediated viral control and mRNA vaccine strategies (1R21AI170246-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10483703. Licensed CC0.

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