# Genetic imprints of therapeutic Ad26/MVA mosaic vaccine in rebound HIV-1 genome from acutely treated individuals

> **NIH NIH R21** · UNIVERSITY OF MARYLAND BALTIMORE · 2020 · $209,617

## Abstract

Summary
Due to the persistent reservoir established soon after HIV-1 transmission, life-long ART
is required to maintain viral load suppression in HIV-1 infected individuals. Development
of strategies able to induce long-term, ART-free remission is a high public health priority.
One important strategy is therapeutic HIV vaccine. Although to date, majority of
therapeutic vaccines failed to show clinical benefit, some showed evidence of vaccine
efficacy as a delayed time to rebound or decreased viral load set point. This provides the
hope to achieve a long-term remission if optimized vaccine strategies can be developed.
The proposed study leverages a highly unique opportunity to employ novel sequencing
technologies to understand viral evolutionary patterns in response to therapeutic
vaccination in a promising Ad26.Mos/MVA.Mos vaccine regimen amongst acutely
treated individuals who underwent analytical treatment interruption (ATI) in the RV405
study. This will be the first HIV-1 genetic study in the setting of a randomized, placebo-
controlled therapeutic vaccine trial. Preliminary analysis showed successfully elicited
immune responses in all RV405 vaccine recipients and a slightly delayed time to viral
load rebound in the vaccine arm. Our central hypothesis is that the immune responses
elicited by Ad26/MVA vaccination will exert selection pressures on the replicating viruses
during rebound, which will leave “genetic imprints” in the rebound viral genomes. Both
the genetic background of the T/F virus and its evolutionary trajectory in response to
vaccine-induced immune pressures will correlate with the vaccine outcomes. We
propose the following specific aims:
Aim 1: To compare the genetic compositions of pre-ART and rebound viral populations
and to identify vaccine-related genetic imprints in rebound viral genomes.
Aim 2: To identify viral genetic correlates of the vaccine outcomes in both the T/F and
rebound viral genomes.
Our long-term goal is to translate knowledge of HIV vulnerabilities into optimizing future
vaccine strategies towards the goal of HIV remission and eradication.

## Key facts

- **NIH application ID:** 10175390
- **Project number:** 7R21AI147893-02
- **Recipient organization:** UNIVERSITY OF MARYLAND BALTIMORE
- **Principal Investigator:** Hongshuo Song
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $209,617
- **Award type:** 7
- **Project period:** 2019-07-08 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10175390

## Citation

> US National Institutes of Health, RePORTER application 10175390, Genetic imprints of therapeutic Ad26/MVA mosaic vaccine in rebound HIV-1 genome from acutely treated individuals (7R21AI147893-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10175390. Licensed CC0.

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