title: Live attenuated influenza A virus vaccine protects against A(H1N1)pdm09 heterologous challenge without vaccine associated enhanced respiratory disease.
abstract: Live-attenuated influenza virus (LAIV) vaccines may provide cross-protection against contemporary influenza A virus (IAV) in swine. Conversely, whole inactivated virus (WIV) vaccines have the potential risk of vaccine-associated enhanced respiratory disease (VAERD) when challenged with IAV of substantial antigenic drift. A temperature sensitive, intranasal H1N2 LAIV was compared to wild type exposure (WT) and an intramuscular WIV vaccine in a model shown to induce VAERD. WIV vaccinated swine challenged with pandemic A/H1N1 (H1N1pdm09) were not protected from infection and demonstrated severe respiratory disease consistent with VAERD. Lung lesions were mild and challenge virus was not detected in the respiratory tract of LAIV vaccinates. High levels of post-vaccination IgG serum antibodies targeting the H1N1pdm09 HA2 stalk domain were exclusively detected in the WIV group and associated with increased H1N1pdm09 virus infectivity in MDCK cells. In contrast, infection-enhancing antibodies were not detected in the serum of LAIV vaccinates and VAERD was not observed.
authors.affiliation: Virus and Prion Research Unit, National Animal Disease Center, USDA, Agricultural Research Service, Ames, IA 50010, USA; Department of Veterinary Diagnostic and Production Animal Medicine, College of Veterinary Medicine, Iowa State University, Ames, IA 50011, USA.
authors.forename: Phillip C
authors.initials: PC
authors.lastname: Gauger
authors.affiliation: Virus and Prion Research Unit, National Animal Disease Center, USDA, Agricultural Research Service, Ames, IA 50010, USA.
authors.forename: Crystal L
authors.initials: CL
authors.lastname: Loving
authors.affiliation: Division of Viral Products, Center for Biologics Evaluation and Research, U.S. Food and Drug Administration, Bethesda, MD 20892, USA.
authors.forename: Surender
authors.initials: S
authors.lastname: Khurana
authors.affiliation: Virus and Prion Research Unit, National Animal Disease Center, USDA, Agricultural Research Service, Ames, IA 50010, USA.
authors.forename: Alessio
authors.initials: A
authors.lastname: Lorusso
authors.affiliation: Department of Veterinary Medicine, University of Maryland, College Park, and Virginia-Maryland Regional College of Veterinary Medicine, College Park, MD 20742, USA.
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Perez
authors.affiliation: Virus and Prion Research Unit, National Animal Disease Center, USDA, Agricultural Research Service, Ames, IA 50010, USA.
authors.forename: Marcus E
authors.initials: ME
authors.lastname: Kehrli
authors.affiliation: Department of Veterinary Microbiology and Preventive Medicine, College of Veterinary Medicine, Iowa State University, Ames, IA 50011, USA.
authors.forename: James A
authors.initials: JA
authors.lastname: Roth
authors.affiliation: Division of Viral Products, Center for Biologics Evaluation and Research, U.S. Food and Drug Administration, Bethesda, MD 20892, USA.
authors.forename: Hana
authors.initials: H
authors.lastname: Golding
authors.affiliation: Virus and Prion Research Unit, National Animal Disease Center, USDA, Agricultural Research Service, Ames, IA 50010, USA. Electronic address: amy.vincent@ars.usda.gov.
authors.forename: Amy L
authors.initials: AL
authors.lastname: Vincent
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000032:analysis / Q000097:blood; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D016207:Cytokines / Q000032:analysis; D004285:Dogs; D005260:Female; D018928:Immunity, Mucosal; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology*; D057221:Influenza A Virus, H1N2 Subtype / Q000276:immunology*; D007252:Influenza Vaccines / Q000276:immunology*; D008168:Lung / Q000473:pathology; D061985:Madin Darby Canine Kidney Cells; D008297:Male; D009976:Orthomyxoviridae Infections / Q000517:prevention & control / Q000662:veterinary* / Q000821:virology; D013552:Swine; D013553:Swine Diseases / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D014132:Trachea / Q000276:immunology / Q000473:pathology; D014613:Vaccines, Attenuated / Q000276:immunology; D015164:Vaccines, Inactivated / Q000276:immunology
chemical_list: D000914:Antibodies, Viral; D016207:Cytokines; D007252:Influenza Vaccines; D014613:Vaccines, Attenuated; D015164:Vaccines, Inactivated
keywords: Enhanced pneumonia; Influenza A; Live attenuated influenza virus; Pandemic H1N1; Swine; Whole inactivated virus