# Multi-Omics Correlates of Therapeutic Vaccine Efficacy

> **NIH NIH P01** · BETH ISRAEL DEACONESS MEDICAL CENTER · 2024 · $251,823

## Abstract

SUMMARY
The goal of therapeutic vaccination is to increase host immune control of HIV-1 to achieve durable virologic
control in the absence of ART, which is defined as a “functional cure”. However, therapeutic vaccine studies in
humans have to date been largely unsuccessful. In contrast, in previous therapeutic vaccination studies in
SIV/SHIV infected non-human primates (NHPs), a subset of animals achieved viral control including reduced
viral levels in lymphoid organs, suggesting an anti-reservoir effect of the interventions. Understanding the
mechanisms underlying therapeutic vaccine efficacy and identifying immune signatures that associate with anti-
reservoir activity in vivo is a fundamental prerequisite towards their optimization for HIV cure.
In Project 2, we hypothesize that combinatorial immunization strategies that result in virological control
induce unique peripheral and tissue immune signatures, including reorganization within viral tissue
reservoirs, which can be identified using spatial multi-omics approaches. We further hypothesize that
such protective immune responses mediate their efficacy primarily in lymphoid tissues. To evaluate these
hypotheses, we propose two Specific Aims:
Aim 1. Identify the immunological correlates of virologic control in SIV/SHIV-infected rhesus macaques
following active and combinatorial immunization strategies. We will perform a comprehensive virologic,
immunologic, and multi-omics analysis of existing specimens from three non-human primate and one clinical
studies study to generate hypotheses regarding correlates of long term vs. short term virologic control.
Aim 2. Define mechanisms of peripheral and tissue viral reservoir control in lymphoid tissues following
therapeutic vaccination of SHIV-infected rhesus macaques. We will perform interventional studies to test
the hypothesis that combinatorial vaccine strategies can induce immune responses that target the viral reservoir
in lymph nodes and gastrointestinal mucosa in SHIV-infected rhesus macaques.
We will apply cutting-edge, high-throughput, multi-omics profiling platforms detailed in Core B (Multi-Omics
Core) to define the impact of therapeutic vaccination. We will then integrate the multi-omics data in Core C
(Computational Analysis Core) to generate a comprehensive landscape and regulatory network of the viral
reservoir and host immune responses following therapeutic vaccination. These data will define the impact of
therapeutic vaccination on the replication-competent viral reservoir at an unprecedented level of resolution,
which will provide critical insights for next generation HIV-1 cure efforts.

## Key facts

- **NIH application ID:** 10886132
- **Project number:** 5P01AI177687-02
- **Recipient organization:** BETH ISRAEL DEACONESS MEDICAL CENTER
- **Principal Investigator:** Boris Dominik Juelg
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $251,823
- **Award type:** 5
- **Project period:** 2023-07-11 → 2028-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10886132

## Citation

> US National Institutes of Health, RePORTER application 10886132, Multi-Omics Correlates of Therapeutic Vaccine Efficacy (5P01AI177687-02). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10886132. Licensed CC0.

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