# Development of an M Protein-Deficient Respiratory Syncytial Virus Vaccine for Aerosolized Vaccination of the Lung

> **NIH NIH R41** · HEARTLAND VACCINES, LLC · 2020 · $158,518

## Abstract

Project Summary/Abstract
Respiratory syncytial virus (RSV) is a major respiratory pathogen in human infants and elderly individuals. RSV
infection is the principal cause of hospitalization of infants, and is a leading cause of infant mortality worldwide.
In elderly adults, RSV infection accounts for 10-15,000 deaths annually in the US alone.
Despite the high impact of RSV, there is presently no licensed vaccine despite decades of attempts.
Inactivated RSV vaccines have resulted in vaccine-enhanced disease in infants, in which vaccinated infants
have developed more severe disease than unvaccinated controls when subsequently infected with RSV
naturally. While live attenuated vaccines have not caused enhanced disease, live vaccines have failed
because of either poor immunogenicity or inadequate attenuation. We have developed a novel live vaccine
(“Mnull RSV”) that appears capable of striking the elusive balance between immunogenicity and safety through
its unique method of construction and delivery.
Mnull RSV has a deletion of the gene for the M protein, which is responsible for reassembly of viral proteins
once a cell is infected. Deletion of the M protein leaves Mnull RSV incapable of replicating beyond the first
cycle, but still able to induce strong antibody responses and protect against an RSV challenge in a relevant
(infant baboon) animal model. Because the entire gene for the M protein has been deleted, Mnull RSV cannot
revert back to the wild type during infection, which is a problem with other live, attenuated mutant vaccines.
Mnull RSV thus holds the advantages of live vaccines (broad humoral and cellular responses without
adjuvants) and yet has a strong safety profile as it cannot re-assemble and spread, and cannot revert to a
more aggressive phenotype.
Having demonstrated successful protection by IP vaccination with an endotracheal tube, Heartland Vaccines
LLC now seeks to demonstrate that we can achieve these results with a delivery mechanism appropriate for
use in humans. Our Phase 1 hypothesis is that IP delivery of liquid Mnull RSV to infant baboons using existing
commercially available nebulizers induces a high level of RSV neutralizing antibody and protective immunity
without adverse clinical symptoms. In Specific Aim 1, we will determine the immunogenicity and optimal dose
regimen of Mnull RSV in infant baboons, administered IP after aerosolization via a nebulizer. In Aim 2, we will
challenge optimally vaccinated infant baboons with a wildtype RSV strain and assess the level of protection. If
successful, Heartland Vaccines plans to exclusively license the Mnull technology (patent application in
progress) and seek Phase II funding to establish protocols toward GMP manufacturing of Mnull RSV, and in
addition, develop a dry powder formula and delivery device for Mnull to better enable storage, distribution, and
worldwide vaccination.

## Key facts

- **NIH application ID:** 10007759
- **Project number:** 5R41AI147787-02
- **Recipient organization:** HEARTLAND VACCINES, LLC
- **Principal Investigator:** Robert C. Welliver
- **Activity code:** R41 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $158,518
- **Award type:** 5
- **Project period:** 2019-09-05 → 2023-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10007759

## Citation

> US National Institutes of Health, RePORTER application 10007759, Development of an M Protein-Deficient Respiratory Syncytial Virus Vaccine for Aerosolized Vaccination of the Lung (5R41AI147787-02). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10007759. Licensed CC0.

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