A new study from a team at The Pirbright Institute, has enabled scientists there to better understand H9N2; a form of avian flu which poses risks to both poultry and human health.
The mapping and analysis of the antigenicity of H9N2 avian influenza virus, will guide surveillance and ensure vaccines are more effective; helping prevent serious outbreaks.
H9N2 leads to significant losses in poultry production across Asia, but also has the potential for creating new viruses which can infect humans; with infections reported across China, Bangladesh and Egypt. It can also act as a donor of genes to other zoonotic avian influenza viruses such as the 1997 Hong Kong H5N1 outbreak, and the recent Chinese H7N9 and H10N8 outbreaks.
The use of vaccines is widespread, but influenza viruses are constantly changing, and so the effectiveness of vaccines is often compromised because of the rapid emergence of antigenic variants.
The research, led by Dr Munir Iqbal, Head of the Institute’s Avian Influenza Virus group in the Avian Viral Diseases Programme, (recently published in Scientific Reports), sought to gain a better understanding of the antigenic sites on the influenza virus major antigen: haemagglutinin.
Haemagglutinin is a glycoprotein on the surface of all influenza viruses which enables the virus to enter host cells. There are at least 18 different types of haemagglutinin (H1-H18) that influenza viruses may possess.
Dr Iqbal 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 that 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."
Researchers generated a panel of nine monoclonal antibodies, against a contemporary Pakistani H9N2 isolate; which represents a major Asian H9N2 viral lineage. Antibodies were characterised in detail and used to select a total of 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.
Dr Iqbal added: “Recently it has been suggested that 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.”
