title: Highly attenuated Bordetella pertussis strain BPZE1 as a potential live vehicle for delivery of heterologous vaccine candidates.
abstract: Bordetella pertussis, the causative agent of whooping cough, is a promising and attractive candidate for vaccine delivery via the nasal route, provided that suitable attenuation of this pathogen has been obtained. Recently, the highly attenuated B. pertussis BPZE1 strain has been described as a potential live pertussis vaccine for humans. We investigated here the use of BPZE1 as a live vehicle for heterologous vaccine candidates. Previous studies have reported the filamentous hemagglutinin (FHA), a major B. pertussis adhesin, as a carrier to express foreign antigens in B. pertussis. In this study, we also examined the BrkA autotransporter as a surface display system. Three copies of the neutralizing peptide SP70 from enterovirus 71 (EV71) were fused to FHA or in the passenger domain of BrkA, and each chimera was expressed in BPZE1. The FHA-(SP70)3 and BrkA-(SP70)3 chimeras were successfully secreted and exposed at the bacterial surface, respectively. Nasal administration of the live recombinant strains triggered a strong and sustained systemic anti-SP70 antibody response in mice, although the titers and neutralizing activities against EV71 were significantly higher in the sera of mice immunized with the BrkA-(SP70)3-producing strain. These data indicate that the highly attenuated BPZE1 strain is a potential candidate for vaccine delivery via the nasal route with the BrkA autotransporter as an alternative to FHA for the presentation of the heterologous vaccine antigens.
authors.affiliation: Immunology Programme and Department of Microbiology, Yong Loo Lin School of Medicine, National University of Singapore, 28 Medical Drive, CeLS #03-06N, Singapore 117456, Singapore.
authors.forename: Si Ying
authors.initials: SY
authors.lastname: Ho
authors.forename: Shi Qian
authors.initials: SQ
authors.lastname: Chua
authors.forename: Damian G W
authors.initials: DG
authors.lastname: Foo
authors.forename: Camille
authors.initials: C
authors.lastname: Locht
authors.forename: Vincent T
authors.initials: VT
authors.lastname: Chow
authors.forename: Chit Laa
authors.initials: CL
authors.lastname: Poh
authors.forename: Sylvie
authors.initials: S
authors.lastname: Alonso
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology; D001425:Bacterial Outer Membrane Proteins / Q000378:metabolism; D001886:Bordetella pertussis / Q000145:classification / Q000235:genetics* / Q000472:pathogenicity; D036022:Capsid Proteins / Q000235:genetics / Q000276:immunology; D029821:Enterovirus A, Human / Q000276:immunology; D017353:Gene Deletion; D008168:Lung / Q000382:microbiology; D051379:Mice; D009698:Nucleoproteins; D014765:Viral Vaccines / Q000008:administration & dosage / Q000235:genetics* / Q000276:immunology*
chemical_list: D001425:Bacterial Outer Membrane Proteins; C090007:BrkA protein, Bordetella pertussis; D036022:Capsid Proteins; D009698:Nucleoproteins; D014765:Viral Vaccines; C090319:peptide 31D