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.