title: Immunogenicity of live attenuated B. pertussis BPZE1 producing the universal influenza vaccine candidate M2e.
abstract: BACKGROUND
  Intranasal delivery of vaccines directed against respiratory pathogens is an attractive alternative to parenteral administration. However, using this delivery route for inactivated vaccines usually requires the use of potent mucosal adjuvants, and no such adjuvant has yet been approved for human use.
  
  
  RESULTS
  We have developed a live attenuated Bordetella pertussis vaccine, called BPZE1, and show here that it can be used to present the universal influenza virus epitope M2e to the mouse respiratory tract to prime for protective immunity against viral challenge. Three copies of M2e were genetically fused to the N-terminal domain of filamentous hemagglutinin (FHA) and produced in recombinant BPZE1 derivatives in the presence or absence of endogenous full-length FHA. Only in the absence of FHA intranasal administration of the recombinant BPZE1 derivative induced antibody responses to M2e and effectively primed BALB/c mice for protection against influenza virus-induced mortality and reduced the viral load after challenge. Strong M2e-specific antibody responses and protection were observed after a single nasal administration with the recombinant BPZE1 derivative, followed by a single administration of M2e linked to a virus-like particle without adjuvant, whereas priming alone with the vaccine strain did not protect.
  
  
  CONCLUSIONS
  Using recombinant FHA-3M2e-producing BPZE1 derivatives for priming and the universal influenza M2e peptide linked to virus-like particles for boosting may constitute a promising approach for needle-free and adjuvant-free nasal vaccination against influenza.
authors.affiliation: Inserm U1019, Lille, France.
authors.forename: Hana
authors.initials: H
authors.lastname: Kammoun
authors.forename: Xavier
authors.initials: X
authors.lastname: Roux
authors.forename: Dominique
authors.initials: D
authors.lastname: Raze
authors.forename: Anne-Sophie
authors.initials: AS
authors.lastname: Debrie
authors.forename: Marina
authors.initials: M
authors.lastname: De Filette
authors.forename: Tine
authors.initials: T
authors.lastname: Ysenbaert
authors.forename: Nathalie
authors.initials: N
authors.lastname: Mielcarek
authors.forename: Xavier
authors.initials: X
authors.lastname: Saelens
authors.forename: Walter
authors.initials: W
authors.lastname: Fiers
authors.forename: Camille
authors.initials: C
authors.lastname: Locht
mesh_terms: D018829:Adhesins, Bacterial / Q000235:genetics / Q000276:immunology*; D000281:Administration, Intranasal; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood*; D001886:Bordetella pertussis / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D007251:Influenza, Human / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D051379:Mice; D008807:Mice, Inbred BALB C; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D012137:Respiratory System / Q000187:drug effects / Q000276:immunology / Q000821:virology; D016019:Survival Analysis; D014611:Vaccination; D014614:Vaccines, Synthetic; D014763:Viral Matrix Proteins / Q000235:genetics / Q000276:immunology*; D010566:Virulence Factors, Bordetella / Q000235:genetics / Q000276:immunology*
chemical_list: D018829:Adhesins, Bacterial; D000914:Antibodies, Viral; D007252:Influenza Vaccines; D011993:Recombinant Fusion Proteins; D014614:Vaccines, Synthetic; D014763:Viral Matrix Proteins; D010566:Virulence Factors, Bordetella; C065273:filamentous hemagglutinin adhesin, Bordetella pertussis
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