# Preclinical Development of Ad26/Env Vaccines for HIV

> **NIH NIH U19** · BETH ISRAEL DEACONESS MEDICAL CENTER · 2022 · $942,991

## Abstract

In our current IPCAVD program (U19 AI096040), we have developed alternative serotype adenovirus vectors,
bioinformatically optimized HIV-1 mosaic antigens, and stable Env gp140 protein immunogens. We have shown
that the Ad26-Env/Gag/Pol prime, Env gp140 protein boost (Ad26/Env) vaccine afforded unprecedented
protective efficacy against acquisition of infection following heterologous SIVmac251 challenges in rhesus
monkeys, as well as robust protection against SHIV-SF162P3 challenges. Protection correlated with
polyfunctional antibody responses as determined by systems serology. We have also advanced the Ad26/Env,
Ad26/MVA, and Ad26/MVA/Env mosaic vaccines into phase 1/2a clinical trials in the United States, East Africa,
South Africa, and Thailand. Over the next 5 years of this IPCAVD program, we propose to define the extent and
mechanism of protection achieved by our lead Ad26/Env vaccine regimen in rhesus monkeys, to advance our
lead vaccine regimen into phase 2b/3 efficacy studies in humans, and to develop an improved next generation
HIV-1 vaccine candidate.
In this Project, we hypothesize that our current Ad26/Env mosaic vaccine as well as simplified vaccine
regimens will protect against SHIVs derived from diverse clades by a consistent mechanism involving
polyfunctional non-neutralizing antibodies. We further hypothesize that a next generation HIV-1 vaccine
candidate that elicits augmented NAb magnitude and breadth will improve protective efficacy against
SHIV challenges in rhesus monkeys. To test these hypotheses we propose the following Specific Aims:
Specific Aim 1. To define the protective efficacy and protective mechanism of our Ad26/Env mosaic vaccine
and simplified vaccine regimens against SHIVs derived from diverse clades in rhesus monkeys
Specific Aim 2. To develop an improved HIV-1 vaccine strategy that elicits augmented NAb responses in rhesus
monkeys

## Key facts

- **NIH application ID:** 10339366
- **Project number:** 5U19AI128751-05
- **Recipient organization:** BETH ISRAEL DEACONESS MEDICAL CENTER
- **Principal Investigator:** Dan H. Barouch
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $942,991
- **Award type:** 5
- **Project period:** 2018-02-01 → 2025-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10339366

## Citation

> US National Institutes of Health, RePORTER application 10339366, Preclinical Development of Ad26/Env Vaccines for HIV (5U19AI128751-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10339366. Licensed CC0.

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