Bordetella pertussis, the etiologic agent of
whooping cough, is a highly infectious human pathogen capable of inducing mucosal and systemic immune responses upon a single
intranasal administration. In an attenuated,
pertussis toxin (PTX)-deficient recombinant form, it may therefore constitute an efficient bacterial vector that is particularly well adapted for the delivery of
heterologous antigens to the respiratory mucosa. Filamentous
hemagglutinin (FHA) has been used as a carrier to present foreign
antigens at the bacterial surface, thereby inducing local, systemic, and protective immune responses to these
antigens in mice. Both full-length and truncated (Fha44) forms of FHA have been used for antigen presentation. To investigate the effect of the carrier (FHA or Fha44) on antibody responses to passenger
antigens, we genetically fused the HtrA
protein of nontypeable Haemophilus influenzae to either FHA form. The fha-htrA and Fha44 gene-htrA hybrids were expressed as single copies inserted into the chromosome of PTX-deficient B.
pertussis. Both chimeras were secreted into the culture supernatants of the recombinant strains and were recognized by anti-FHA and anti-HtrA
antibodies. Intranasal
infection with the strain producing the FHA-HtrA hybrid led to significantly higher anti-HtrA and anti-FHA antibody titers than those obtained in mice infected with the Fha44-HtrA-producing strain. Interestingly, the B.
pertussis strain producing the Fha44-HtrA chimera colonized the mouse lungs more efficiently than the parental, Fha44-producing strain and gave rise to higher anti-FHA antibody titers than those induced by the parental strain.