# Durable vaginal protection from HIV via mRNA expression of bnAbs

> **NIH NIH R01** · GEORGIA INSTITUTE OF TECHNOLOGY · 2020 · $729,421

## Abstract

Project summary
In spite of the major advances in the development of effective anti-HIV drugs, currently some 2 million new
infections still occur annually worldwide and over 95% via heterosexual contact. While prevention measures
have made progress, such as PrEP, these measures are frequently either ignored, misused, or often non-
negotiable for the female partner. Thus, providing choices for prevention of infection that are female controlled
will be an asset in the fight to curb the rate of new infections worldwide. With the recent explosion of broadly
neutralizing antibodies (bnAbs) from HIV infected patients, several have been used to demonstrate prevention
of virus acquisition, even when administered post exposure. Unfortunately, vaccines have so far fallen short of
inducing bnAbs, and though topically delivered bnAbs have shown protection, such protection has to date shown
limited durability. To that end, a novel approach for expressing antibodies, with surprisingly long kinetics, in the
female reproductive tract (FRT) via synthetic mRNA was recently demonstrated. Delivery was achieved through
direct, rapid, aerosol exposure of the FRT epithelium to naked mRNA in water. Persistence of the antibody was
achieved through the incorporation of a GPI-linker into the heavy chain. In rhesus macaques, the ability to
protect macaque FRT explants from SHIV infection ex vivo has been shown. The long-term goal is to develop
a cost-effective mRNA-based approach for expressing bnAbs in the FRT, providing a new paradigm for
generating anti-infection barriers at the mucosal port(s) of entry. The short-term goals are to optimize the
delivery, longevity and protective efficacy of bnAbs against SHIV infections of rhesus macaques by: 1) optimizing
the delivery approach and protocol such that we have efficient transfection of the vaginal and cervical epithelium,
2) optimization of the antibody linker strategy to promote long-term expression in macaques, and 3) testing of
single antibodies and combinations, including bi-specific antibodies. The efficacy of the optimization will be
tested in a true challenge study in the macaque model. If successful, design information vital for making a proper
device for delivering mRNA to the FRT in humans will be provided, and sufficient pre-clinical data in support of
a future FDA IND application.

## Key facts

- **NIH application ID:** 10160529
- **Project number:** 1R01AI155007-01A1
- **Recipient organization:** GEORGIA INSTITUTE OF TECHNOLOGY
- **Principal Investigator:** PHILIP J SANTANGELO
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $729,421
- **Award type:** 1
- **Project period:** 2020-09-16 → 2021-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10160529

## Citation

> US National Institutes of Health, RePORTER application 10160529, Durable vaginal protection from HIV via mRNA expression of bnAbs (1R01AI155007-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10160529. Licensed CC0.

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