# Establishing a relevant mouse model with susceptibility to non-adapted influenza viruses for vaccine challenge studies

> **NIH NIH R21** · OHIO STATE UNIVERSITY · 2020 · $185,264

## Abstract

SUMMARY
Influenza virus infection is a major health concern worldwide. Our best defense against seasonal influenza
virus infections is vaccination, but current vaccine strategies are not fully effective and may not offer protection
against viruses that emerge from animals. One impediment to the development of better vaccines is the lack of
a tractable and cost-effective small animal model for testing new vaccine technology. Mice are ubiquitously
used in research, but influenza viruses that infect humans often require adaptation in order to infect and cause
pathology in mice. This requirement for virus adaptation limits the utility of the mouse model for testing human
vaccine candidates in challenge studies with relevant non-adapated human viruses. However, we found that
mice engineered to lack a critical antiviral restriction factor known as interferon-induced transmembrane protein
3 (IFITM3) show increased susceptibility to a variety of influenza virus strains, including human isolates that
otherwise do not cause significant pathology in wild type mice. We propose that IFITM3 knockout mice may
thus serve as a long-sought mouse model for influenza virus vaccine testing. We will test whether these mice
possess the two characteristics needed in a pre-clinical testing model: 1) Whether IFITM3 knockout mice
possess the ability to mount protective adaptive immune responses upon vaccination, and 2) Whether IFITM3
knockout mice are fully susceptible to a wide breadth of human and animal-derived influenza viruses. In
addition to allowing more rapid and cost-effective testing of new seasonal and universal influenza virus
vaccines, this research will also provide insights into humans who possess IFITM3 defects in terms of virus
susceptibility and the ability to counteract this immunodeficiency with vaccination.

## Key facts

- **NIH application ID:** 9960085
- **Project number:** 1R21AI151230-01
- **Recipient organization:** OHIO STATE UNIVERSITY
- **Principal Investigator:** Jacob Yount
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $185,264
- **Award type:** 1
- **Project period:** 2020-07-06 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9960085

## Citation

> US National Institutes of Health, RePORTER application 9960085, Establishing a relevant mouse model with susceptibility to non-adapted influenza viruses for vaccine challenge studies (1R21AI151230-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9960085. Licensed CC0.

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