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 antiHtrA 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.The mucosal delivery of vaccines has several advantages over systemic delivery. Consequently, the development of efficient mucosal vaccine delivery systems, including live attenuated or commensal bacterial vaccines, has attracted much attention over the last decades. However, most efforts have so far been devoted to the oral route, although the oral delivery of vaccine formulations requires large quantities of antigen and repeated administrations to be effective. The nasal route may represent an interesting alternative (23), as it avoids the encounter with an acidic and proteolytic environment as well as the competition with commensal microorganisms present in the digestive tract.Bordetella pertussis, the etiologic agent of whooping cough, has recently been used as a live vector to deliver foreign antigens to the respiratory mucosa in laboratory models (29). As a highly contagious agent, it colonizes the human respiratory tract very efficiently and induces both local and systemic immune responses. The deletion of the genes encoding pertussis toxin (PTX), the major virulence factor of B. pertussis (24), has led to a highly attenuated strain, as evidenced by a strong reduction in lung inflammation and lymphocytosis (18). In this genetically attenuated form, B. pertussis is able to induce strong protection against respiratory challenges with virulent strains when given by the nasal route in a...