The vaccine potential of Bordetella pertussis biofilm-derived membrane proteins

Abstract

Pertussis is an infectious respiratory disease of humans caused by the gram-negative pathogen Bordetella pertussis. The use of acellular pertussis vaccines (aPs) which induce immunity of relative short duration and the emergence of vaccine-adapted strains are thought to have contributed to the recent resurgence of pertussis in industrialized countries despite high vaccination coverage. Current pertussis vaccines consist of antigens derived from planktonic bacterial cultures. However, recent studies have shown that biofilm formation represents an important aspect of B. pertussis infection, and antigens expressed during this stage may therefore be potential targets for vaccination. Here we provide evidence that vaccination of mice with B. pertussis biofilm-derived membrane proteins protects against infection. Subsequent proteomic analysis of the protein content of biofilm and planktonic cultures yielded 11 proteins which were ≥three-fold more abundant in biofilms, of which Bordetella intermediate protein A (BipA) was the most abundant, surface-exposed protein. As proof of concept, mice were vaccinated with recombinantly produced BipA. Immunization significantly reduced colonization of the lungs and antibodies to BipA were found to efficiently opsonize bacteria. Finally, we confirmed that bipA is expressed during respiratory tract infection of mice, and that anti-BipA antibodies are present in the serum of convalescent whooping cough patients. Together, these data suggest that biofilm proteins and in particular BipA may be of interest for inclusion into future pertussis vaccines.

Proteomic Adaptation of Australian Epidemic Bordetella pertussis

“…BipA is a biofilm‐derived protein that is thought to be involved in transmission and/or adhesion . Deletion of BipA in Bordetella bronchiseptica and B. pertussis showed no significant difference in colonization ability, however BipA can be highly immunogenic . Downregulation of BipA may allow current B. pertussis strains to hide from immune recognition without affecting colonization ability.…”

Hijacking Complement Regulatory Proteins for Bacterial Immune Evasion

“…Complement evasion molecules fulfill most, if not all, of these criteria. Studies show immunogenicity of multiple complement evasion molecules in vaccination models including B. pertussis Vag8, S. pneumoniae PspC and S. aureus SdrE (Stranger-Jones et al, 2006; Ferreira et al, 2009; de Gouw et al, 2014). Furthermore, the vast majority of the complement evasion molecules described in this review are expressed by most, if not all, virulent strains of one particular bacterial species and the proteins are highly conserved (Bhattacharjee et al, 2013; Fleury et al, 2014; de Gouw et al, 2014; Hallström et al, 2015).…”

Bordetella adenylate cyclase toxin interacts with filamentous haemagglutinin to inhibit biofilm formation in vitro

“…Ongoing studies support the concept that B. pertussis forms biofilm during infection; recent clinical isolates form more biofilm compared to a lab‐passaged isolate, BP338, and de Gouw et al . showed that biofilm‐derived antigens protect mice from B. pertussis infection (de Gouw et al ., ; Arnal et al ., ). The closely related animal pathogen, B. bronchiseptica forms biofilm in vitro on abiotic surfaces and biofilm formation contributes to its chronic infection of dogs and other mammals (Fenwick, ).…”