title: Multivalent HA DNA vaccination protects against highly pathogenic H5N1 avian influenza infection in chickens and mice.
abstract: BACKGROUND
  Sustained outbreaks of highly pathogenic avian influenza (HPAI) H5N1 in avian species increase the risk of reassortment and adaptation to humans. The ability to contain its spread in chickens would reduce this threat and help maintain the capacity for egg-based vaccine production. While vaccines offer the potential to control avian disease, a major concern of current vaccines is their potency and inability to protect against evolving avian influenza viruses.
  The ability of DNA vaccines encoding hemagglutinin (HA) proteins from different HPAI H5N1 serotypes was evaluated for its ability to elicit neutralizing antibodies and to protect against homologous and heterologous HPAI H5N1 strain challenge in mice and chickens after DNA immunization by needle and syringe or with a pressure injection device. These vaccines elicited antibodies that neutralized multiple strains of HPAI H5N1 when given in combinations containing up to 10 HAs. The response was dose-dependent, and breadth was determined by the choice of the influenza virus HA in the vaccine. Monovalent and trivalent HA vaccines were tested first in mice and conferred protection against lethal H5N1 A/Vietnam/1203/2004 challenge 68 weeks after vaccination. In chickens, protection was observed against heterologous strains of HPAI H5N1 after vaccination with a trivalent H5 serotype DNA vaccine with doses as low as 5 microg DNA given twice either by intramuscular needle injection or with a needle-free device.
  
  
  CONCLUSIONS
  DNA vaccines offer a generic approach to influenza virus immunization applicable to multiple animal species. In addition, the ability to substitute plasmids encoding different strains enables rapid adaptation of the vaccine to newly evolving field isolates.
authors.affiliation: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America.
authors.forename: Srinivas
authors.initials: S
authors.lastname: Rao
authors.forename: Wing-Pui
authors.initials: WP
authors.lastname: Kong
authors.forename: Chih-Jen
authors.initials: CJ
authors.lastname: Wei
authors.forename: Zhi-Yong
authors.initials: ZY
authors.lastname: Yang
authors.forename: Martha
authors.initials: M
authors.lastname: Nason
authors.forename: Darrel
authors.initials: D
authors.lastname: Styles
authors.forename: Louis J
authors.initials: LJ
authors.lastname: DeTolla
authors.forename: Aruna
authors.initials: A
authors.lastname: Panda
authors.forename: Erin M
authors.initials: EM
authors.lastname: Sorrell
authors.forename: Haichen
authors.initials: H
authors.lastname: Song
authors.forename: Hongquan
authors.initials: H
authors.lastname: Wan
authors.forename: Gloria C
authors.initials: GC
authors.lastname: Ramirez-Nieto
authors.forename: Daniel
authors.initials: D
authors.lastname: Perez
authors.forename: Gary J
authors.initials: GJ
authors.lastname: Nabel
mesh_terms: D000818:Animals; D002645:Chickens; D006388:Hemagglutinins / Q000235:genetics*; D053124:Influenza A Virus, H5N1 Subtype / Q000276:immunology*; D007252:Influenza Vaccines / Q000008:administration & dosage*; D005585:Influenza in Birds / Q000517:prevention & control*; D051379:Mice; D016896:Treatment Outcome; D019444:Vaccines, DNA / Q000008:administration & dosage*
chemical_list: D006388:Hemagglutinins; D007252:Influenza Vaccines; D019444:Vaccines, DNA