Immunodominant Domains Present on theBordetella pertussisVaccine Component Filamentous Hemagglutinin

Abstract

To identify immunologically important domains on filamentous hemagglutinin (FHA), a Bordetella pertussis protein included in new acellular pertussis vaccines (ACPVs), a series of monoclonal antibodies, sera from infants vaccinated with ACPVs or whole cell pertussis vaccine (WCPV), and sera from patients with pertussis were analyzed by immunoblots containing FHA fragments and recombinant FHA proteins. Immunodominant domains located at the COOH-terminus of FHA (type I domain) and near the NH2-terminus (type II domain) were defined by the reactivity with monoclonal antibodies. The sera from patients with pertussis and sera from infants vaccinated with WCPV or with 6 different investigational ACPVs specifically recognized well-defined regions within the type I and type II domains. Identification of these prominent immunologic epitopes on FHA should be useful for the construction of more well-defined pertussis vaccines and for the interpretation of human serologic responses, which may correlate with efficacy of pertussis vaccines.

Eighty-Kilodalton N-Terminal Moiety of Bordetella pertussis Filamentous Hemagglutinin: Adherence, Immunogenicity, and Protective Role

“…Since in vitro studies have shown that Fha44 is secreted at high levels and is surface associated (34), it should be accessible to the immune system of the host, unless secretion or surface display of Fha44 differs dramatically between in vitro-and in vivo-growing B. pertussis. Furthermore, infection of mice or children with wild-type B. pertussis producing fulllength FHA results in the generation of anti-Fha44 antibodies (20), although the major antigenic determinants of FHA are located in its C-terminal moiety, which is absent in Fha44. This indicates that the Fha44 portion of FHA is immunoaccessible in the context of B. pertussis infection.…”

“…In addition, most anti-FHA antibodies are directed against its C-terminal moiety (9,20,28,42). The N-terminal moiety, essentially the Fha44 domain, contains only minor B-cell epitopes (20). It is conceivable that the protective epitopes of FHA are located not in the immunodominant domain but rather in the Fha44 region.…”

“…It has been postulated that an effective antibody response to FHA, which interferes with the attachment of the bacteria to the respiratory mucosal surface, could prevent infection (4). The C-terminal moiety of mature FHA has been demonstrated to be the immunodominant part of the protein (9,20,28,42). It also contains most of the cell-binding sites.…”

Subcutaneous Vaccination with Attenuated Salmonella enterica Serovar Choleraesuis C500 Expressing Recombinant Filamentous Hemagglutinin and Pertactin Antigens Protects Mice against Fatal Infections with both S. enterica Serovar Choleraesuis and Bordetella bronchiseptica

“…The pertactin protein has two repeated regions, regions 1 and 2; region 2 is identified as being an immunodominant protective epitope (4). The filamentous hemagglutinin (FHA) of B. pertussis is defined as being an important attachment factor and protective immunogen (28,36), with two main immunodominant regions, identified as type I and type II domains (8,20). In addition, the individual type I domain of FHA induced an immune response that protected BALB/c mice against intranasal (i.n.)…”

Enhanced bacterial virulence through exploitation of host glycosaminoglycans

“…This domain is also one of the two immunodominant domains of FHA (Leininger et al, 1997). Both Bordetella bronchiseptica and Bordetella parapertussis express FHA-like molecules (Cotter et al, 1998).…”