Use of Bordetella pertussis as a live delivery vehicle: Exploring different carrier systems to display an enterovirus 71 vaccine candidate

Abstract

Attenuated Bordetella pertussis represents a promising candidate for nasal delivery of heterologous vaccine antigens. Filamentous hemagglutinin, a major B. pertussis adhesin, has so far been used as the carrier, inducing local and systemic murine immune responses against the heterologous antigen upon nasal administration of the live recombinant bacteria. This project has investigated the B. pertussis autotransporter BrkA as carrier to expose foreign antigens at the bacterial surface. We fused three copies of the neutralizing peptide SP70 from the Enterovirus 71 VP1 capsid protein within the BrkA passenger domain and expressed this in a highly attenuated B. pertussis strain. A recombinant with three copies of SP70 inserted in FHA was also constructed. Both BrkA-(SP70)3 and FHA-(SP70)3 chimera were successfully surface-exposed and secreted respectively. Nasal administration of the former triggered significantly higher murine anti-SP70 neutralizing titers than the latter, clearly indicating BrkAb s potential as a heterologous antigen carrier in attenuated B. pertussis.