# Effect of host immunity stimulated by viral IL-10-deleted RhCMV vaccines on SIV rebound

> **NIH NIH P01** · UNIVERSITY OF CALIFORNIA AT DAVIS · 2020 · $690,805

## Abstract

HIV rebound after interruption of anti-retroviral therapy (ART) is generally thought to reflect the size of the
persistent reservoir found in long-lived memory CD4+ T cells, with a smaller reservoir reflected in delayed
rebound. However, tissue reservoirs under ART suppression have been poorly characterized, so we do not
know if characteristics of those reservoirs have a dominant impact on rebound kinetics. The contribution of
host immune responses to rebound kinetics is also poorly understood, especially since most available data are
focused on IFN-γ producing T cell responses that are not related to control of viral load in acute or chronic
infection. It would be surprising if the indiscriminate total of such responses had an important impact on
rebound.
Project 2 will leverage unique advantages of the rhesus macaque model to understand how tissue
reservoirs and host immunity impact rebound. The animal model will provide frequent longitudinal samples
of tissue-resident cells and recrudescent virus throughout suppressive ART and during rebound, which will be
characterized by Dr. Mario Stevenson under the auspices of Project 3. In addition, we have the unique
capability in rhesus macaques to induce both Mamu-E-restricted CD8+ T cells and memory NK cells using viral
IL-10-deleted RhCMV/SIV vaccines. In contrast to conventional class Ia-restricted CD8+ T cells expressing
IFN-γ,1,2 Mamu-E-restricted CD8+ T cells likely contribute to suppression and even elimination of virus soon
after infection, when SIV is replicating quickly in T cells, many of which are confined to gut tissue. We propose
that the situation in a human patient after ART withdrawal is similar to that early stage of infection, in that HIV
rebound presumably begins from a small number of cells reactivating virus in restricted anatomic sites. Thus,
if HLA-E-restricted responses are present in some human patients (Project 1) or can be induced in vaccinated
humans or macaques, these individuals might exhibit delayed rebound.
We hypothesize that the unique immune responses elicited by RhCMV/SIV therapeutic vaccination under ART,
but not conventional CTL elicited by Ad/SIV vaccine when used alone, alter both tissue viral reservoirs and SIV
rebound kinetics. Our specific aims are: 1. Test if therapeutic RhCMV/SIV vaccination is superior to Ad/SIV
vaccination for depletion of the Tfh-resident SIV reservoir. 2. Test if RhCMV/SIV vaccination slows rebound
kinetics. 3. Determine if HLA/Mamu-E-restricted T cell responses are induced in unvaccinated individuals by
CMV co-infection and are a biomarker for delayed rebound.

## Key facts

- **NIH application ID:** 9963121
- **Project number:** 5P01AI131568-04
- **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:** 2020
- **Award amount:** $690,805
- **Award type:** 5
- **Project period:** 2017-07-19 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9963121

## Citation

> US National Institutes of Health, RePORTER application 9963121, Effect of host immunity stimulated by viral IL-10-deleted RhCMV vaccines on SIV rebound (5P01AI131568-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9963121. Licensed CC0.

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