title: Vaccine-associated enhanced respiratory disease is influenced by haemagglutinin and neuraminidase in whole inactivated influenza virus vaccines.
abstract: Multiple subtypes and many antigenic variants of influenza A virus (IAV) co-circulate in swine in the USA, complicating effective use of commercial vaccines to control disease and transmission. Whole inactivated virus (WIV) vaccines may provide partial protection against IAV with substantial antigenic drift, but have been shown to induce vaccine-associated enhanced respiratory disease (VAERD) when challenged with an antigenic variant of the same haemagglutinin (HA) subtype. This study investigated the role the immune response against HA, neuraminidase (NA) and nucleoprotein (NP) may play in VAERD by reverse engineering vaccine and challenge viruses on a common backbone and using them in a series of vaccination/challenge trials. Mismatched HA between vaccine and challenge virus was necessary to induce VAERD. However, vaccines containing a matched NA abrogated the VAERD phenomenon induced by the HA mismatch and this was correlated with NA-inhibiting (NI) antibodies. Divergence between the two circulating swine N2 lineages (92 % identity) resulted in a loss of NI cross-reactivity and also resulted in VAERD with the mismatched HA. The NP lineage selected for use in the WIV vaccine strains did not affect protection or pathology. Thus the combination of HA and NA in the vaccine virus strains played a substantial role in vaccine protection versus immunopathology, suggesting that vaccines that target the HA protein alone could be more prone to VAERD due to the absence of cross-protective NI antibodies.
authors.affiliation: Virus and Prion Diseases of Livestock Research Unit, National Animal Disease Center, USDA, Agricultural Research Service, Ames, IA, USA.
authors.forename: Daniela S
authors.initials: DS
authors.lastname: Rajão
authors.affiliation: Department of Veterinary Medicine, University of Maryland, College Park, and Virginia-Maryland Regional College of Veterinary Medicine, College Park, MD, USA.
authors.forename: Hongjun
authors.initials: H
authors.lastname: Chen
authors.affiliation: Department of Veterinary Medicine, University of Maryland, College Park, and Virginia-Maryland Regional College of Veterinary Medicine, College Park, MD, USA.
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Perez
authors.affiliation: Department of Veterinary Microbiology and Preventive Medicine, Iowa State University, Ames, IA, USA.
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Sandbulte
authors.affiliation: Department of Veterinary Diagnostic and Production Animal Medicine, Iowa State University, Ames, IA, USA.
authors.forename: Phillip C
authors.initials: PC
authors.lastname: Gauger
authors.affiliation: Virus and Prion Diseases of Livestock Research Unit, National Animal Disease Center, USDA, Agricultural Research Service, Ames, IA, USA.
authors.forename: Crystal L
authors.initials: CL
authors.lastname: Loving
authors.affiliation: Australian Army Malaria Institute, Enoggera, QLD, Australia.
authors.forename: G Dennis
authors.initials: GD
authors.lastname: Shanks
authors.affiliation: Virus and Prion Diseases of Livestock Research Unit, National Animal Disease Center, USDA, Agricultural Research Service, Ames, IA, USA.
authors.forename: Amy
authors.initials: A
authors.lastname: Vincent
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000276:immunology; D000914:Antibodies, Viral / Q000276:immunology; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000276:immunology; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology*; D057221:Influenza A Virus, H1N2 Subtype / Q000276:immunology*; D053122:Influenza A Virus, H3N2 Subtype / Q000276:immunology*; D007252:Influenza Vaccines / Q000009:adverse effects* / Q000276:immunology*; D009439:Neuraminidase / Q000276:immunology; D009698:Nucleoproteins / Q000276:immunology; D009976:Orthomyxoviridae Infections / Q000276:immunology / Q000517:prevention & control / Q000821:virology*; D012137:Respiratory System / Q000821:virology; D013552:Swine; D013553:Swine Diseases / Q000276:immunology / Q000517:prevention & control / Q000821:virology*; D014611:Vaccination; D015164:Vaccines, Inactivated / Q000009:adverse effects / Q000276:immunology
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D007252:Influenza Vaccines; D009698:Nucleoproteins; D015164:Vaccines, Inactivated; D009439:Neuraminidase