I’ve been working with collaborators at the University of Glasgow and the Avian Influenza Group at the Pirbright Institute on the genetic basis of antigenic variation among avian influenza viruses. We’ve uploaded a manuscript to bioRxiv on “The molecular basis of A(H9N2) avian influenza viruses”. Thomas Peacock and I share the lead authorship on this work, we’ve used a combination of experimental and computational approaches to explore the genetic basis of immune escape by these viruses.
A(H9N2) viruses are an economically important pathogen of poultry across much of Asia, the Middle East, and North and West Africa. They play a crucial role at the human-animal interface, particularly in China where they are the most common flu subtype in poultry. A(H9N2) viruses pose a threat to human health, both as a zoonotic agent in their own right, but also as an important donor of genes to novel reassortant viruses that may infect humans.
Like other flu subtypes, vaccine effectiveness is persistently challenged by the emergence of novel antigenic variants. Current understanding of antigenic variation among A(H9N2) viruses is largely derived from a handful of monoclonal antibody (mAb) escape mutant studies. These studies have identified a variety of amino acid substitutions that allow mutant viruses to grow in the presence of an antibody that targets a specific area of the virus.
Our main findings:
- Many mAb escape mutations are absent, or very rare, among sequenced A(H9N2) viruses.
- Several others had no significant effect on chicken antisera binding (mutations that result in extra glycosylation were a notable exception).
- Modelling antigenic and genetic data from circulating viruses identifies several novel amino acid substitutions that could explain antigenic variation in the field.
- Substitutions enabling immune escape by increasing glycosylation or receptor-binding avidity had the largest impacts on chicken antisera binding.
- Modelling and examination of sequence data suggests that of these two mechanisms of immune escape, modulation of avidity likely plays a greater role in evolution in nature.