title: Construction and Immunogenicity Evaluation of Recombinant Influenza A Viruses Containing Chimeric Hemagglutinin Genes Derived from Genetically Divergent Influenza A H1N1 Subtype Viruses.
abstract: OBJECTIVE
  Influenza A viruses cause highly contagious diseases in a variety of hosts, including humans and pigs. To develop a vaccine that can be broadly effective against genetically divergent strains of the virus, in this study we employed molecular breeding (DNA shuffling) technology to create a panel of chimeric HA genes.
  
  
  RESULTS
  Each chimeric HA gene contained genetic elements from parental swine influenza A viruses that had a history of zoonotic transmission, and also from a 2009 pandemic virus. Each parental virus represents a major phylogenetic clade of influenza A H1N1 viruses. Nine shuffled HA constructs were initially screened for immunogenicity in mice by DNA immunization, and one chimeric HA (HA-129) was expressed on both a A/Puerto Rico/8/34 backbone with mutations associated with a live, attenuated phenotype (PR8LAIV-129) and a A/swine/Texas/4199-2/98 backbone (TX98-129). When delivered to mice, the PR8LAIV-129 induced antibodies against all four parental viruses, which was similar to the breadth of immunity observed when HA-129 was delivered as a DNA vaccine. This chimeric HA was then tested as a candidate vaccine in a nursery pig model, using inactivated TX98-129 virus as the backbone. The results demonstrate that pigs immunized with HA-129 developed antibodies against all four parental viruses, as well as additional primary swine H1N1 influenza virus field isolates.
  
  
  CONCLUSIONS
  This study established a platform for creating novel genes of influenza viruses using a molecular breeding approach, which will have important applications toward future development of broadly protective influenza virus vaccines.
authors.affiliation: Division of Basic Biomedical Sciences, Sanford School of Medicine, The University of South Dakota, Vermillion, SD, 57069, United States of America.
authors.forename: Kara
authors.initials: K
authors.lastname: McCormick
authors.affiliation: Department of Veterinary and Biomedical Sciences, South Dakota State University, Brookings, SD, 57007, United States of America.
authors.forename: Zhiyong
authors.initials: Z
authors.lastname: Jiang
authors.affiliation: Department of Veterinary and Biomedical Sciences, South Dakota State University, Brookings, SD, 57007, United States of America.
authors.forename: Longchao
authors.initials: L
authors.lastname: Zhu
authors.affiliation: Department of Veterinary and Biomedical Sciences, South Dakota State University, Brookings, SD, 57007, United States of America.
authors.forename: Steven R
authors.initials: SR
authors.lastname: Lawson
authors.affiliation: Department of Veterinary and Biomedical Sciences, South Dakota State University, Brookings, SD, 57007, United States of America.
authors.forename: Robert
authors.initials: R
authors.lastname: Langenhorst
authors.affiliation: Department of Veterinary and Biomedical Sciences, South Dakota State University, Brookings, SD, 57007, United States of America.
authors.forename: Russell
authors.initials: R
authors.lastname: Ransburgh
authors.affiliation: Division of Basic Biomedical Sciences, Sanford School of Medicine, The University of South Dakota, Vermillion, SD, 57069, United States of America.
authors.forename: Colin
authors.initials: C
authors.lastname: Brunick
authors.affiliation: Division of Basic Biomedical Sciences, Sanford School of Medicine, The University of South Dakota, Vermillion, SD, 57069, United States of America.
authors.forename: Miranda C
authors.initials: MC
authors.lastname: Tracy
authors.affiliation: Division of Basic Biomedical Sciences, Sanford School of Medicine, The University of South Dakota, Vermillion, SD, 57069, United States of America.
authors.forename: Heather R
authors.initials: HR
authors.lastname: Hurtig
authors.affiliation: Division of Basic Biomedical Sciences, Sanford School of Medicine, The University of South Dakota, Vermillion, SD, 57069, United States of America.
authors.forename: Leah M
authors.initials: LM
authors.lastname: Mabee
authors.affiliation: Division of Basic Biomedical Sciences, Sanford School of Medicine, The University of South Dakota, Vermillion, SD, 57069, United States of America.
authors.forename: Mark
authors.initials: M
authors.lastname: Mingo
authors.affiliation: Department of Veterinary and Biomedical Sciences, South Dakota State University, Brookings, SD, 57007, United States of America.
authors.forename: Yanhua
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, TN, 38105, United States of America.
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Webby
authors.affiliation: Division of Basic Biomedical Sciences, Sanford School of Medicine, The University of South Dakota, Vermillion, SD, 57069, United States of America.
authors.forename: Victor C
authors.initials: VC
authors.lastname: Huber
authors.affiliation: Department of Veterinary and Biomedical Sciences, South Dakota State University, Brookings, SD, 57007, United States of America.
authors.forename: Ying
authors.initials: Y
authors.lastname: Fang
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D032621:DNA Shuffling; D005260:Female; D050939:Gene Fusion; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000235:genetics* / Q000276:immunology; D007114:Immunization; D053118:Influenza A Virus, H1N1 Subtype / Q000235:genetics* / Q000276:immunology; D007252:Influenza Vaccines / Q000235:genetics / Q000276:immunology*; D051379:Mice; D034421:Sus scrofa / Q000276:immunology / Q000821:virology
chemical_list: D000914:Antibodies, Viral; C543345:H1N1 virus hemagglutinin; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D007252:Influenza Vaccines