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PhD Defence: Broadening the antiviral landscape for influenza A virus

On 29 February, Mirte Pascha successfully defended her thesis entitled: ‘Broadening the antiviral landscape for influenza A virus- Glycoprotein-targeted approaches to infection prevention and treatment’ at Utrecht University. The potential of influenza A virus (IAV) to evolve and cross species barriers keeps it at the forefront of public health concerns. The endemic seasonal viruses are associated with a consistently high disease burden, and zoonotic infections pose a continuous threat of sparking the next pandemic.

The influenza A virus is a highly contagious virus that can cause respiratory infections leading to severe complications in risk groups. Current strategies for preventing and treating influenza consist of vaccines and antiviral medications. Although these agents can be reasonably effective, their efficacy is hindered by the virus’s ability to continually adapt, leading to the development of resistance.

The research explored various strategies to develop more broad-spectrum vaccines and therapies. The focus is on the glycoproteins on the virus’s surface: the receptor-binding and fusion protein hemagglutinin (HA) and the receptor-cleaving enzyme neuraminidase (NA). By placing the NA protein on nanoparticles, it elicited a stronger antibody response and provided better protection against influenza virus infection in mice. After vaccination with these NA nanoparticles, we also further investigated the antibodies formed to gain a better understanding of how they bind and protect.

Finally, we discovered peptide-based inhibitors against HA that bind to a conserved part of the protein, providing broad protection against various virus strains.

This research offers additional insights and innovative strategies that could contribute to the development of more effective interventions against the influenza A virus.

More about this project

Development of novel broadly protective anti-influenza virus strategies – NCOH