# Pushing HIV-1 Vaccine Protection to the Mucosal Barrier

> **NIH NIH R56** · MAYO CLINIC ROCHESTER · 2024 · $745,752

## Abstract

Abstract
Most gene-based vaccines are replication-defective mRNA, DNA, or adenovirus (Ad) vaccines. In each case,
the vaccine delivers its one copy of an antigen gene and expresses "1X" of the antigens that are encoded by the
vaccine. We developed single cycle Ad (SC-Ad) vaccines that replicate vaccine antigen genes up to 10,000-fold
in every cell to amplify antigen production but do not produce infectious progeny viruses. When RD-Ad and SC-
Ad6 expressing HIV-1 antigens or SARS-CoV-2 spike are compared, SC-Ad produces 100 times more antigen
than RD-Ad and generates significantly higher antibodies than RD-Ad-Spike or mRNA vaccines. When spike-
immunized animals were challenged 10.5 months after single immunization, SC-Ad reduced SARS-CoV-2 lung
viral loads and damage and preserved body weights better than RD-Ad.
During the COVID-19 pandemic, we tested SC-Ads expressing SIV gag and clade C HIV-1 Env in rhesus
macaques by intramuscular (IM), intranasal (IN), and intravaginal (IVAG) routes of immunization in combination
with IM co-immunization with adjuvanted clade C SOSIP protein. When the macaques were challenged vaginally
with clade C SHIV.CH505.375H.dCT 1.5 years after last vaccine, PBS, IN, and IM vaccinated animals became
infected with similar kinetics with only one IN animal resisting infection. In contrast, 50% of the IVAG macaques
resisted vaginal challenge.
These data suggest there are great merits to creating a mucosal barrier against incoming SHIV at the site of viral
entry. Given this, this project will determine the reproducibility of this protection and examine how vaginal
immunization drives local-regional immune responses in the female reproductive tract (FRT) and if these
responses might be amplified by co-immunization in this site.
Proof of concept here for being able to “push” immune responses into the FRT in macaques will allow these
approaches to be translated for humans, to protect not just women, but all sexes and gender identities from
vaginal, rectal, or penile exposures to HIV-1.

## Key facts

- **NIH application ID:** 11113407
- **Project number:** 1R56AI184121-01A1
- **Recipient organization:** MAYO CLINIC ROCHESTER
- **Principal Investigator:** Michael A Barry
- **Activity code:** R56 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $745,752
- **Award type:** 1
- **Project period:** 2024-07-19 → 2026-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11113407

## Citation

> US National Institutes of Health, RePORTER application 11113407, Pushing HIV-1 Vaccine Protection to the Mucosal Barrier (1R56AI184121-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/11113407. Licensed CC0.

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