title: Cold-adapted influenza and recombinant adenovirus vaccines induce cross-protective immunity against pH1N1 challenge in mice.
abstract: BACKGROUND
  The rapid spread of the 2009 H1N1 pandemic influenza virus (pH1N1) highlighted problems associated with relying on strain-matched vaccines. A lengthy process of strain identification, manufacture, and testing is required for current strain-matched vaccines and delays vaccine availability. Vaccines inducing immunity to conserved viral proteins could be manufactured and tested in advance and provide cross-protection against novel influenza viruses until strain-matched vaccines became available. Here we test two prototype vaccines for cross-protection against the recent pandemic virus.
  
  
  RESULTS
  BALB/c and C57BL/6 mice were intranasally immunized with a single dose of cold-adapted (ca) influenza viruses from 1977 or recombinant adenoviruses (rAd) expressing 1934 nucleoprotein (NP) and consensus matrix 2 (M2) (NP+M2-rAd). Antibodies against the M2 ectodomain (M2e) were seen in NP+M2-rAd immunized BALB/c but not C57BL/6 mice, and cross-reacted with pH1N1 M2e. The ca-immunized mice did not develop antibodies against M2e. Despite sequence differences between vaccine and challenge virus NP and M2e epitopes, extensive cross-reactivity of lung T cells with pH1N1 peptides was detected following immunization. Both ca and NP+M2-rAd immunization protected BALB/c and C57BL/6 mice against challenge with a mouse-adapted pH1N1 virus.
  
  
  CONCLUSIONS
  Cross-protective vaccines such as NP+M2-rAd and ca virus are effective against pH1N1 challenge within 3 weeks of immunization. Protection was not dependent on recognition of the highly variable external viral proteins and could be achieved with a single vaccine dose. The rAd vaccine was superior to the ca vaccine by certain measures, justifying continued investigation of this experimental vaccine even though ca vaccine is already available. This study highlights the potential for cross-protective vaccines as a public health option early in an influenza pandemic.
authors.affiliation: Division of Cellular and Gene Therapies, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, Maryland, United States of America.
authors.forename: Mark R
authors.initials: MR
authors.lastname: Soboleski
authors.forename: Jon D
authors.initials: JD
authors.lastname: Gabbard
authors.forename: Graeme E
authors.initials: GE
authors.lastname: Price
authors.forename: Julia A
authors.initials: JA
authors.lastname: Misplon
authors.forename: Chia-Yun
authors.initials: CY
authors.lastname: Lo
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Perez
authors.forename: Jianqiang
authors.initials: J
authors.lastname: Ye
authors.forename: S Mark
authors.initials: SM
authors.lastname: Tompkins
authors.forename: Suzanne L
authors.initials: SL
authors.lastname: Epstein
mesh_terms: D000222:Adaptation, Physiological / Q000276:immunology*; D000256:Adenoviridae / Q000276:immunology*; D000595:Amino Acid Sequence; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D003080:Cold Temperature; D056738:Cross Protection / Q000276:immunology*; D000939:Epitopes / Q000737:chemistry / Q000276:immunology; D007109:Immunity / Q000276:immunology*; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology*; D007252:Influenza Vaccines / Q000276:immunology*; D008168:Lung / Q000276:immunology / Q000473:pathology / Q000821:virology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009976:Orthomyxoviridae Infections / Q000097:blood / Q000453:epidemiology / Q000276:immunology / Q000821:virology; D058873:Pandemics; D013601:T-Lymphocytes / Q000276:immunology; D014611:Vaccination; D014614:Vaccines, Synthetic / Q000276:immunology*; D019562:Viral Load / Q000276:immunology
chemical_list: D000914:Antibodies, Viral; D000939:Epitopes; D007252:Influenza Vaccines; D014614:Vaccines, Synthetic