A versatile H5N1-VSV platform for safe influenza virus research applications
Boopathi Sownthirarajan1, Maya Mason1, Gayathri Loganathan1
1Department of Microbiology and Immunology, University of Iowa, Iowa City, Iowa, USA.
Journal of Virology
|August 8, 2025
Summary
A novel vesicular stomatitis virus (VSV)-based vaccine expressing H5N1 influenza A virus (IAV) genes provides a safe and effective platform for studying H5N1 IAV and developing new influenza vaccines.
Area of Science:
- Virology
- Immunology
- Vaccinology
Background:
- Highly pathogenic H5N1 influenza A virus (IAV) poses a significant threat to avian, mammalian, and human health, necessitating research under stringent Biosafety Level 3 (BSL-3) conditions.
- Vesicular stomatitis virus (VSV)-based vaccine vectors have demonstrated safety and efficacy in preclinical and clinical studies for various viral pathogens.
- Developing safe and adaptable research tools is crucial for understanding and combating emerging H5N1 IAV strains.
Discussion:
- A recombinant VSV expressing H5N1 IAV hemagglutinin (HA) and neuraminidase (NA) genes (H5N1-VSV) was developed as a versatile research platform.
- H5N1-VSV exhibited robust replication in cell lines, comparable to the wild-type H5N1 virus.
- The study identified antigenic site Sa polymorphisms in H5N1 strains from cattle under immune pressure, mirroring pandemic IAV evolution in humans.
Key Insights:
- H5N1-VSV vaccination in mice was safe, induced robust immunity, and conferred protection against a contemporary H5N1 strain.
- This VSV-based platform allows for studying H5N1 IAV biology without requiring BSL-3 containment for the full virus.
- The emergence of H5N1 polymorphisms highlights the importance of continuous surveillance and adaptable vaccine strategies.
Outlook:
- H5N1-VSV represents a promising, adaptable platform for influenza research and vaccine development.
- Further studies can explore the potential of H5N1-VSV in diverse animal models and for evaluating different vaccine formulations.
- This platform could accelerate the development of countermeasures against H5N1 and other emerging influenza viruses.


