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Studentship: Identification of genetic markers in the haemagglutinin glycoprotein critical for antigenic activity of H9N2 avian influenza viruses

Reference	BBS/E/I/00001759
Principal Investigator / Supervisor	Professor Munir Iqbal
Co-Investigators / Co-Supervisors
Institution	The Pirbright Institute
Department	The Pirbright Institute Department
Funding type	Research
Value (£)	115,670
Status	Completed
Type	Institute Project
Start date	01/10/2012
End date	30/09/2016
Duration	47 months

Abstract

Studentship: H9N2 avian influenza (AI) viruses are endemic in poultry in many countries. They pose a serious threat to poultry and are also recognised as a threat to human health. The impact of these viruses can be minimised by efficacious vaccines and diagnostics. The efficacy of these tools is continually compromised by the emergence of antigenic variants due to genetic drift in the HA glycoprotein. Recently we identified that neither recombinant HA nor whole virus antigens belonging to two different H9N2 virus strains had antigenic cross-reactivity using chicken antisera. Consequently, a vaccine based on one strain would be unable to induce cross-protective immune responses to the other strain, despite belonging to same subtype. Similarly, reagents for serological diagnostic analysis also become redundant. Comparison of the sequence of the HA1 polypeptide of each strain revealed that there were at least 10 distinct genetic motifs between them. These finding gave us an opportunity for detailed analysis of each differing amino acid or combination of amino acid motifs that are potentially implicated in the diversity of antigenic specificity and cross-reactivity of these H9N2 viruses. A number of recombinant mutant haemagglutinin (HA) glycoproteins and AI viruses will be produced, based on the distinct amino acid variations observed between the two H9N2 viruses. These will be characterised by haemagglutination inhibition (HI), enzyme-linked immunosorbent assay (ELISA), virus neutralization (VN) tests, western blot, surface plasmon resonance (SPR) and nanoparticle tracking analysis (NTA). The outcomes will be used to establish a direct correlation between substitutions in HA that result in loss of antigenic cross-reactivity or decrease in antigen-antibody binding affinity of variant viruses. This knowledge will contribute to more efficacious vaccines and diagnostic tools to reduce the impact of influenza viruses in animals and humans.

Summary

unavailable

Committee	Not funded via Committee
Research Topics	Animal Health, Immunology, Microbiology
Research Priority	X – Research Priority information not available
Research Initiative	X - not in an Initiative
Funding Scheme	X – not Funded via a specific Funding Scheme

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