title: Mutations in the haemagglutinin protein and their effect in transmission of highly pathogenic avian influenza (HPAI) H5N1 virus in sub-optimally vaccinated chickens.
abstract: Transmission of highly pathogenic avian influenza (HPAI) viruses in poultry flocks is associated with huge economic losses, culling of millions of birds, as well as human infections and deaths. In the cases where vaccination against avian influenza is used as a control measure, it has been found to be ineffective in preventing transmission of field strains. Reports suggest that one of the reasons for this is the use of vaccine doses much lower than the ones recommended by the manufacturer, resulting in very low levels of immunity. In a previous study, we selected for immune escape mutants using homologous polyclonal sera and used them as vaccines in transmission experiments. We concluded that provided a threshold of immunity is reached, antigenic distance between vaccine and challenge strains due to selection need not result in vaccine escape. Here, we evaluate the effect that the mutations in the haemagglutinin protein of our most antigenically-distant mutant may have in the transmission efficiency of this mutant to chickens vaccinated against the parent strain, under sub-optimal vaccination conditions resembling those often found in the field.
  
  
  
  In this study we employed reverse genetics techniques and transmission experiments to examine if the HA mutations of our most antigenically-distant mutant affect its efficiency to transmit to vaccinated chickens. In addition, we simulated sub-optimal vaccination conditions in the field, by using a very low vaccine dose.
  
  
  
  We find that the mutations in the HA protein of our most antigenically-distant mutant are not enough to allow it to evade even low levels of vaccination-induced immunity.
  
  
  
  Our results suggest that - for the antigenic distances we investigated - vaccination can reduce transmission of an antigenically-distant strain compared to the unvaccinated groups, even when low vaccine doses are used, resulting in low levels of immunity.
authors.affiliation: Quantitative Veterinary Epidemiology, Department of Animal Sciences, Wageningen University, Radix Building 107, Droevendaalsesteeg 1, 6708 PB Wageningen, The Netherlands; Department of Virology, Central Veterinary Institute of Wageningen University and Research Centre, Houtribweg 39, 8221 RA Lelystad, The Netherlands. Electronic address: ioannis.sitaras@wur.nl.
authors.forename: Ioannis
authors.initials: I
authors.lastname: Sitaras
authors.affiliation: Quantitative Veterinary Epidemiology, Department of Animal Sciences, Wageningen University, Radix Building 107, Droevendaalsesteeg 1, 6708 PB Wageningen, The Netherlands.
authors.forename: Xanthoula
authors.initials: X
authors.lastname: Rousou
authors.affiliation: Department of Virology, Central Veterinary Institute of Wageningen University and Research Centre, Houtribweg 39, 8221 RA Lelystad, The Netherlands.
authors.forename: Ben
authors.initials: B
authors.lastname: Peeters
authors.affiliation: Quantitative Veterinary Epidemiology, Department of Animal Sciences, Wageningen University, Radix Building 107, Droevendaalsesteeg 1, 6708 PB Wageningen, The Netherlands. Electronic address: mart.dejong@wur.nl.
authors.forename: Mart C M
authors.initials: MCM
authors.lastname: de Jong
mesh_terms: D000818:Animals; D002645:Chickens; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000235:genetics*; D053124:Influenza A Virus, H5N1 Subtype / Q000235:genetics / Q000472:pathogenicity*; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000276:immunology; D005585:Influenza in Birds / Q000276:immunology / Q000517:prevention & control / Q000635:transmission*; D009154:Mutation; D011201:Poultry Diseases / Q000276:immunology / Q000517:prevention & control / Q000821:virology; D059386:Reverse Genetics; D014611:Vaccination / Q000662:veterinary*; D064166:Vaccine Potency
chemical_list: D019267:Hemagglutinin Glycoproteins, Influenza Virus; D007252:Influenza Vaccines
keywords: Epidemiology; H5N1; HA; Influenza; Mutations; Transmission; Vaccination