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.
Abstract:
The H5N1 strain of influenza A virus (IAV) continues to cause severe infections in a range of avian and mammalian species, including sporadic but concerning cases in humans. There is growing concern that circulating H5N1 strains could lead to widespread human outbreaks. Research with highly pathogenic H5N1 viruses is restricted to Biosafety Level 3 (BSL-3) laboratories. Vesicular stomatitis virus (VSV)-based vaccine vectors expressing heterologous viral proteins from Ebola, SARS-CoV-2, Lassa virus, etc., have previously been shown to be safe and effective in animal models and human clinical trials. Here, we report the development of a recombinant VSV expressing the hemagglutinin (HA) and neuraminidase (NA) genes of H5N1 IAV (H5N1-VSV), which serves as a versatile platform to study various aspects of H5N1 IAV biology. H5N1-VSV replicated robustly to titers comparable to those of the full H5N1 virus in multiple cell lines. In mice, H5N1-VSV vaccination was safe, elicited strong immunity, and conferred protection against a circulating H5N1 strain. Notably, we found that polymorphisms in antigenic site Sa of circulating strains emerged under immune selection pressure in cattle, resembling the evolution of pandemic IAV in humans. These findings suggest that H5N1-VSV can serve as a safe, adaptable platform for influenza research.
Insights
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.
