# Phase I therapeutic testing of viral-vectored vaccines that shift CD8+ T cell immunodominance to conserved regions of HIV-1

> **NIH NIH U01** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2020 · $1,279,617

## Abstract

1.2 million Americans are currently infected with human immunodeficiency virus-1 (HIV). The advent of
combination antiretroviral therapy (cART) successfully contains viral proliferation, preserving CD4+ T cell
counts and prolonging life. However, HIV infection is still associated with significant stigmatization, and life-long
cART treatment, in an ageing population, bears significant societal health costs. ‘HIV cure’ is defined as
therapies to take HIV infected individuals off life-long cART. Cure would not only have societal and economic
benefits but would also be a critical advance in ending the global HIV epidemic. The challenge for HIV curative
strategies is that long-lived resting cells, principally CD4+ T cells, harbor replication-competent virus which can
stochastically reactivate. The result is that, for most people, interruption of cART results in HIV rebound within
weeks. Curative strategies for HIV largely involve combination therapies, drugs to drive reactivation of HIV and
immune-based therapies to detect and clear the reactivated cells. In this study, we propose a first-in-human
trial of a novel vaccine regimen which aims to elicit an arm of our immune response, called CD8+ T
cells. CD8+ T cells are very effective at detecting virus infected cells. The vaccine regimen called,
ChAdOx1.tHIVconsv5–MVA.tHIVconsv3 was developed by our collaborator at the University of Oxford. A
previous iteration of this vaccine induced very high CD8+ T cells against HIV. The key features of this vaccine
is that it shifts the T cell response to conserved HIV regions that limit the ability of HIV to evade the immune
response. In this study, HIV infected durably suppressed participants will be sequentially vaccinated with
ChAdOx1.tHIVconsv5 and MVA.tHIVconsv3. We will thoroughly characterize the safety profile of these
vaccines. We will also use standardized assays to measure the level of T cells induced by vaccination and
investigate whether vaccination has any impact on very low levels of HIV in our participants. Exploratory
studies will examine whether we can detect vaccine-induced T cells that target HIV in lymph nodes and also
whether checkpoint inhibitor molecules can be used in concert with vaccination to maximize T cell function.
The first vaccine study will be followed by a second related study. The second study builds on the first, by
examining whether mosaic vaccines (vaccines designed to increase coverage of HIV) can further improve on
the conserved immunogen design of ChAdOx1.tHIVconsv5–MVA.tHIVconsv3.

## Key facts

- **NIH application ID:** 9948561
- **Project number:** 5U01AI131310-04
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** Nilu Goonetilleke
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $1,279,617
- **Award type:** 5
- **Project period:** 2017-07-20 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9948561

## Citation

> US National Institutes of Health, RePORTER application 9948561, Phase I therapeutic testing of viral-vectored vaccines that shift CD8+ T cell immunodominance to conserved regions of HIV-1 (5U01AI131310-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9948561. Licensed CC0.

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