# An immunodominance-based Pan-Pneumovirus vaccine for protection against RSV and hMPV

> **NIH NIH R01** · FLORIDA STATE UNIVERSITY · 2024 · $690,023

## Abstract

The goal of this research project is to further the development of a pan-Pneumovirus vaccine and to test our
hypothesis that a chimeric Pneumovirus fusion (F) protein vaccine displaying immunodominant epitopes of
respiratory syncytial virus (RSV) and human metapneumovirus (hMPV) will induce broad protection against both
viruses. RSV and hMPV are widely prevalent agents of childhood viral respiratory infection, causing thousands
of deaths and hundreds of thousands of hospitalizations each year. There are currently no approved vaccines
to elicit protective antibodies against either virus, and no specific treatment options are available. The F
glycoproteins of RSV and hMPV have been well-studied as targets of neutralizing antibodies, and several
vaccine candidates for RSV are in clinical trials. We have developed a novel vaccine candidate (RHMS-1)
encompassing immunodominant epitopes of both RSV and hMPV F proteins and verified its protective
efficacy in mouse and cotton rat models. The rationale for pursuing a chimeric vaccine candidate is based
on several factors, including focusing the immune response to only those epitopes that elicit potent neutralizing
antibodies rather than less potent or non-neutralizing epitopes to improve protection, reducing vaccine escape
compared to previous chimeric vaccines incorporating a single epitope, and the assessment of the first chimeric
vaccine candidate beyond the mouse model. Additionally, we will determine immune correlates of protection for
hMPV infection in a nonhuman primate model. These critical studies will provide a wealth of immunologic
information in highly relevant, pre-clinical models that will guide an evidence-based path toward the optimization
of a safe and effective pan-Pneumovirus vaccine. Our research will substantially advance the field by
developing a vaccine for protection against the two leading causes of acute lower respiratory tract infection in
children. As the pre-fusion RSV F protein has already demonstrated safety and the ability to elicit an effective
immune response, we will build upon this success to extend this vaccine for protection against hMPV. In Aim 1,
we will computationally stabilize and redesign our vaccine candidate, RHMS-1, using Rosetta to enhance protein
stability and immunogenicity, and the best candidates will be rapidly screened in mice as both protein subunit
and mRNA-lipid nanoparticle vaccines. In Aim 2, we will conduct structural and epitope analysis of our top
vaccine candidate to verify the epitopes on RHMS are similar to RSV F and hMPV F proteins. In Aim 3, we will
determine the protective efficacy of the top candidate RHMS vaccine in cotton rat and African Green Monkey
models of RSV and hMPV infection. Our proposal is both conceptually and practically innovative as we are
designing and testing novel vaccine candidates for protection against two important respiratory pathogens, and
we are challenging current paradigms in the field by providing a single an...

## Key facts

- **NIH application ID:** 10861035
- **Project number:** 5R01AI173416-03
- **Recipient organization:** FLORIDA STATE UNIVERSITY
- **Principal Investigator:** Jarrod Mousa
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $690,023
- **Award type:** 5
- **Project period:** 2023-06-06 → 2028-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10861035

## Citation

> US National Institutes of Health, RePORTER application 10861035, An immunodominance-based Pan-Pneumovirus vaccine for protection against RSV and hMPV (5R01AI173416-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10861035. Licensed CC0.

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