# Safety and Immunogenicity of H3N2 M2SR monovalent influenza vaccine in older subjects

> **NIH NIH U01** · FLUGEN, INC. · 2021 · $1,301,311

## Abstract

Respiratory infections with influenza viruses cause severe morbidity and mortality in humans
and animals worldwide. Importantly, in humans, the majority of morbidity and mortality following
flu infection is seen in older individuals (> 65 years old). Yet, clear understanding of how aging
impacts on immune responses, and how to improve vaccine design in this age group is lacking.
Restimulating preexisting memory T cells against conserved epitopes in influenza virus by a
vaccine might confer protective immunity in this age group. An ideal vaccine for elderly should
therefore engage pattern recognition receptors (PRRs) that activate antigen-presenting cells
(APCs), generate conserved antigenic epitopes, while avoiding overt inflammatory responses.
We have demonstrated that ex-vivo stimulation with M2SR virus results in robust restimulation
of memory CD4 and CD8 T cells in older humans without causing pathological inflammation by
engaging non-inflammasome dependent innate pathways. We have shown in a Phase 1a
clinical study that M2SR is generally safe and well-tolerated with the ability to elicit immune
responses in seronegative, seropositive and seroprotected subjects. Subsequently, we showed
that M2SR recipients provided protection against a highly drifted influenza virus. In this
proposal, we will explore the ability of M2SR to stimulate antiviral immune responses in older
subjects in the following aims:
Aim 1. Conduct Phase 1b study testing safety and immunogenicity of M2SR in older
subjects.
Aim 2. Evaluate immune responses from older human subjects vaccinated with M2SR
These experiments are aimed at improving protection of older humans from influenza-mediated
disease, by understanding the immune responses that contribute to protective immunity. The
outcome of the experiments is expected to have high impact with respect to the fundamental
understanding of the ability of M2SR to elicit immune responses in the susceptible elderly
population, and in demonstrating safety of an effective vaccine dosing regimen.

## Key facts

- **NIH application ID:** 10246781
- **Project number:** 5U01AI141310-02
- **Recipient organization:** FLUGEN, INC.
- **Principal Investigator:** Pamuk Bilsel
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $1,301,311
- **Award type:** 5
- **Project period:** 2020-08-25 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10246781

## Citation

> US National Institutes of Health, RePORTER application 10246781, Safety and Immunogenicity of H3N2 M2SR monovalent influenza vaccine in older subjects (5U01AI141310-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10246781. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*