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Developing a Pandemic Influenza Vaccine

Principal Supervisor: Dr Craig Thompson

Secondary Supervisor(s): Dr Nicole Robb

University of Registration: University of Warwick

BBSRC Research Themes: Understanding the Rules of Life (Immunology, Microbiology, Structural Biology)

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Deadline: 4 January, 2024


Project Outline

Influenza often undergoes zoonotic transfer – moving from an animal reservoir to a human host - causing pandemics. Influenza has caused four pandemics due to zoonotic transfer since 1918. In 1918-1922, the ‘Spanish flu’ pandemic killed 50-100 million people, in 1957 the ‘Asian flu’ pandemic caused 1 million deaths, in 1968 ‘Hong Kong’ flu pandemic causes 1 million deaths, and in 2009 ‘swine flu’ caused an estimated 300,000 deaths worldwide [1]. Future pandemics will occur and zoonotic transfer is likely to become a greater issue as humans continue to encroach on animal habitats [2]. 

Currently, three influenza strains circulate in the human population: H1N1 and H3N2 influenza A as well as a lineage of influenza B. Influenza A strains of particular concern that might cause the next pandemic are the H2, H5, H7 and H9 subtypes of influenza, which are currently circulating in pigs and birds [3].  

We have found that immunity due to circulating influenza A in the human population has produced a cross-reactive immune response to these exotic potential pandemic H2, H5, H7 and H9 influenza A strains found in pigs and birds.  

In this project, we propose to characterise the immunity to these potential pandemic strains in humans, pig and birds to determine the location of epitopes responsible for the observed immunity, before combining the identified epitopes into a vaccine to protect against potential pandemic influenza using cutting-edge nanoparticle vaccine vector technology.  

To do this, we will use structural bioinformatics and phylogenetic to identify key cross-reactive epitopes. We will then use pseudotyped virus and live influenza virus microneutralisation assays in combination with site-directed mutagenesis to determine their cross-reactivity against a panel of influenza strains. Pulldown experiments and in vivo immunisation and challenge of mice will also be used to define epitope sequence and cross-reactivity [3].

References

1. Nat Rev Dis Primers 2018 4; 2. Infect Ecol Epidemiol. 2011 1; 3. Vaccines 2021 9(6

Techniques

  • CL2 and CL3 virus culture
  • Bioinformatics
  • Molecular Biology (e.g. cloning, PCR, plasmid digestion, western blotting, qRT-PCR, RNA synthesis, protein cross-linking)