Bordetella pertussis filamentous hemagglutinin: evaluation as a protective antigen and colonization factor in a mouse respiratory infection model

Abstract

Filamentous hemagglutinin (FHA) is a cell surface protein of Bordetella pertussis which functions as an adhesin for this organism. It is a component of many new acellular pertussis vaccines. The proposed role of FHA in immunity to pertussis is based on animal studies which have produced some conflicting results. To clarify this situation, we reexamined the protective activity of FHA in an adult mouse respiratory infection model. Four-week-old BALB/c mice were immunized with one or two doses of 4 or 8 micrograms of FHA and then aerosol challenged with B. pertussis Tohama I. In control mice receiving tetanus toxoid, the CFU in the lungs increased from 10(5) immediately following infection to greater than 10(6) by days 5 and 9 after challenge. Mice immunized with FHA by the intraperitoneal or intramuscular route had significantly reduced bacterial colonization in the lungs. A decrease in colonization of the trachea was also observed in FHA-immunized mice. Evaluation of antibody responses in these mice revealed high titers of immunoglobulin G (IgG) and IgM to FHA in sera and of IgG to FHA in lung lavage fluids. No IgA to FHA was detected. BALB/c mice were also passively immunized intravenously with either goat or rat antibodies to FHA and then aerosol challenged 24 h later, when anti-FHA antibodies were detected in the respiratory tract. Lung and tracheal colonization was markedly reduced in mice immunized with FHA-specific antibodies compared with those receiving control antibodies. In additional studies, the role of FHA in the colonization of the mouse respiratory tract was evaluated by using strain BP101, an FHA mutant of B. pertussis. FHA was important in the initial colonization of the mouse trachea, but was not required for colonization of the trachea later in the infection. FHA was not a factor in colonization of the lungs. Collectively, these experiments demonstrate (i) that systemic immunization with FHA can provide significant protection against B. pertussis infection in both the lower and upper respiratory tract of mice as defined by the lungs and trachea, respectively; (ii) that this protection is mediated primarily by serum antibodies to FHA, which transudate into respiratory secretions; and (iii) that FHA is an important upper respiratory tract colonization factor. These studies provide further evidence for the role of FHA in pertussis pathogenesis and immunity.