Identification and characterization of App: an immunogenic autotransporterprotein of Neisseria meningitidis

In a search for immunogenic virulence factors in Neisseria meningitidis, we have identified a gene encoding a predicted 160 kDa protein with homology to the autotransporter family of proteins. Members of this family are secre ted or surface exposed and are often associated with virulence in Gram-nega tive bacterial pathogens. We named the gene adhesion and penetration protei n (app), because of (it) over bars extensive homology to the hap gene of Ha emophilus influenzae. We reconstructed the gene with reference to genomic s equence data and cloned and expressed the protein in Escherichia coli. Rabb it antiserum raised against recombinant App reacted with proteins in all me ningococcal isolates examined, which represented clonal groups responsible for the majority of meningococcal invasive disease. Antibodies to the prote in were detected in the sera of patients convalescing from meningococcal in fection. Purified App had strong stimulating activity for T cells isolated from a number of healthy donors and from one convalescent patient. We confi rmed that App is surface localized, cleaved and secreted by N. meningitidis . Importantly, the rabbit anti-App serum killed the organism in the presenc e of complement. Thus, App is conserved among meningococci, immunogenic in humans and potentially involved in virulence. It therefore merits further i nvestigation as a component of a future multivalent vaccine.