title: A cell culture-derived whole-virus H5N1 vaccine induces long-lasting cross-clade protective immunity in mice which is augmented by a homologous or heterologous booster vaccination.
abstract: BACKGROUND
  Preparation for an H5N1 influenza pandemic in humans could include priming the population in the pre-pandemic period with a vaccine produced from an existing H5N1 vaccine strain, with the possibility of boosting with a pandemic virus vaccine when it becomes available. We investigated the longevity of the immune response after one or two priming immunizations with a whole-virus H5N1 vaccine and the extent to which this can be boosted by later immunization with either a homologous or heterologous vaccine.
  
  
  METHODS
  Mice received one or two priming immunizations with a Vero cell culture-derived, whole-virus clade 1 H5N1 vaccine formulated to contain either 750 ng or 30 ng hemagglutinin. Six months after the first priming immunization, mice received either a booster immunization with the same clade 1 vaccine or a heterologous clade 2.1 vaccine, or buffer. Humoral and cellular immune responses were evaluated before and at regular intervals after immunizations. Three weeks after booster immunization, mice were challenged with a lethal dose of wild-type H5N1 virus from clades 1, 2.1 or 2.2 and survival was monitored for 14 days.
  
  
  RESULTS
  One or two priming immunizations with the 750 ng or 30 ng HA formulations, respectively, induced H5N1-neutralizing antibody titers which were maintained for ≥ 6 months and provided long-term cross-clade protection against wild-type virus challenge. Both humoral and cellular immune responses were substantially increased by a booster immunization after 6 months. The broadest protective immunity was provided by an immunization regimen consisting of one or two priming immunizations with a clade 1 vaccine and a boosting immunization with a clade 2.1 vaccine.
  
  
  CONCLUSIONS
  These data support the concept that pre-pandemic vaccination can provide robust and long-lasting H5N1 immunity which could be effectively boosted by immunization either with another pre-pandemic vaccine or with the pandemic strain vaccine.
authors: Vaccine R&D, Baxter BioScience, Biomedical Research Centre, Uferstraße 15, A-2304 Orth/Donau, Austria.
authors: Nicolas
authors: N
authors: Sabarth
authors: Helga
authors: H
authors: Savidis-Dacho
authors: Michael G
authors: MG
authors: Schwendinger
authors: Peter
authors: P
authors: Brühl
authors: Daniel
authors: D
authors: Portsmouth
authors: Brian A
authors: BA
authors: Crowe
authors: Otfried
authors: O
authors: Kistner
authors: P Noel
authors: PN
authors: Barrett
authors: Thomas R
authors: TR
authors: Kreil
authors: M Keith
authors: MK
authors: Howard
mesh_terms: D000818:Animals; D000910:Antibodies, Heterophile; D057134:Antibodies, Neutralizing; D002522:Chlorocebus aethiops; D003429:Cross Reactions / Q000276:immunology; D004306:Dose-Response Relationship, Immunologic; D005260:Female; D007111:Immunity, Cellular / Q000276:immunology; D056724:Immunity, Humoral; D007115:Immunization Schedule; D007117:Immunization, Secondary; D053124:Influenza A Virus, H5N1 Subtype / Q000276:immunology* / Q000472:pathogenicity; D007252:Influenza Vaccines / Q000008:administration & dosage* / Q000276:immunology*; D051379:Mice; D014709:Vero Cells / Q000821:virology
chemical_list: D000910:Antibodies, Heterophile; D057134:Antibodies, Neutralizing; D007252:Influenza Vaccines