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.

• biofilms
• BipA
• Bordetella pertussis
• proteomics
• vaccination

We thank Maurice van Dael en Jolein Gloerich (Radboud Proteomics Centre, Radboud University Medical Centre, Nijmegen, The Netherlands) for technical assistance regarding proteomics experiments and Fred van Opzeeland, Elles Simonetti and Saskia van Selm (Laboratory of Pediatric Infectious Diseases, Department of Pediatrics, Radboud university medical center, Nijmegen, The Netherlands; Laboratory of Medical Immunology, Department of Laboratory Medicine, Radboud University Medical Center, Nijmegen, The Netherlands) for assistance with the animal experiments. We thank Guy Berbers (Netherlands Centre for Infectious Disease Control, National Institute for Public Health and the Environment) for human sera. Daan de Gouw is supported by Grant 125020001 from the Netherlands Organization of Scientific Research (ZonMw).

Supplementary Information for this article can be found on Emerging Microbes & Infections' website (http://www.nature.com/emi/).