A study from a team at The Pirbright Institute has enabled scientists to better understand H9N2 – a form of avian flu that poses risks to poultry and human health.

bird flu
H9N2 leads to significant losses in poultry production across Asia, but also has the potential for creating new viruses that can infect humans. Image: Tentacle / Fotolia.

It is believed the mapping and analysis of the antigenicity of the H9N2 virus will guide surveillance and allow for the creation of more effective vaccines, helping prevent serious outbreaks.

Antigenic understanding

The research sought to gain a better understanding of the antigenic sites on the influenza virus major antigen haemagglutinin – a glycoprotein on the surface of all influenza viruses that enables the virus to enter host cells.

Munir Iqbal, head of Pirbright’s avian influenza virus group in the avian viral diseases programme, said: “During circulation in birds, the virus acquires genetic changes in the haemagglutinin gene that greatly influence its antigenic properties, resulting in viruses with the ability to escape natural or vaccine-induced immunity. This means vaccines can fail in the field and lead to viruses circulating and spreading unhindered in vaccinated animals.

“To increase the effectiveness of vaccines, we needed to understand more about the molecular factors that allow these viruses to escape from vaccine-induced immunity, as well as a better awareness of how a more potent, cross-protective immune response may be induced.”

The science

Munir Iqbal
Munir Iqbal. Image: The Pirbright Institute.

Researchers generated a panel of nine monoclonal antibodies against a contemporary Pakistani H9N2 isolate. Antibodies were characterised in detail and used to select 26 unique “escape” mutants with substitutions across nine different amino acid residues in haemagglutinin, including seven that have not been described as antigenic determinants for H9N2 viruses before.

The analysis and structural mapping revealed two novel antigenic sites: “H9-A” and “H9-B”.

Additionally, a second subset of escape mutants contained amino acid deletions within the haemagglutinin receptor binding site. This constitutes a novel method of escape for this group of haemagglutinins and could represent an alternative means for H9N2 viruses to overcome vaccine-induced immunity.

Enabling more accurate vaccine matching

Dr Iqbal added: “It has been suggested the most effective method of preventing new zoonotic avian influenza subtypes from entering the human population would be better control of these viruses in poultry.

“This research gives us a better understanding of the basis of antigenicity of these viruses, and will enable more accurate vaccine matching with circulating field strains with veterinary or human pandemic potential.

“It will also help virus surveillance efforts determine that antigenic variants are emerging or prevalent in a population.”


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