title: Previously unrecognized vaccine candidates against group B meningococcus identified by DNA microarrays.
abstract: We have used DNA microarrays to follow Neisseria meningitidis serogroup B (MenB) gene regulation during interaction with human epithelial cells. Host-cell contact induced changes in the expression of 347 genes, more than 30% of which encode proteins with unknown function. The upregulated genes included transporters of iron, chloride, amino acids, and sulfate, many virulence factors, and the entire pathway of sulfur-containing amino acids. Approximately 40% of the 189 upregulated genes coded for peripherally located proteins, suggesting that cell contact promoted a substantial reorganization of the cell membrane. This was confirmed by fluorescence activated cell sorting (FACS) analysis on adhering bacteria using mouse sera against twelve adhesion-induced proteins. Of the 12 adhesion-induced surface antigens, 5 were able to induce bactericidal antibodies in mice, demonstrating that microarray technology is a valid approach for identifying new vaccine candidates and nicely complements other genome mining strategies used for vaccine discovery.
authors.affiliation: Chiron SpA, Via Fiorentina 1, 53100 Siena, Italy.
authors.forename: Renata
authors.initials: R
authors.lastname: Grifantini
authors.forename: Erika
authors.initials: E
authors.lastname: Bartolini
authors.forename: Alessandro
authors.initials: A
authors.lastname: Muzzi
authors.forename: Monia
authors.initials: M
authors.lastname: Draghi
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Frigimelica
authors.forename: Joel
authors.initials: J
authors.lastname: Berger
authors.forename: Giulio
authors.initials: G
authors.lastname: Ratti
authors.forename: Roberto
authors.initials: R
authors.lastname: Petracca
authors.forename: Giuliano
authors.initials: G
authors.lastname: Galli
authors.forename: Mauro
authors.initials: M
authors.lastname: Agnusdei
authors.forename: Marzia Monica
authors.initials: MM
authors.lastname: Giuliani
authors.forename: Laura
authors.initials: L
authors.lastname: Santini
authors.forename: Brunella
authors.initials: B
authors.lastname: Brunelli
authors.forename: Hervé
authors.initials: H
authors.lastname: Tettelin
authors.forename: Rino
authors.initials: R
authors.lastname: Rappuoli
authors.forename: Filippo
authors.initials: F
authors.lastname: Randazzo
authors.forename: Guido
authors.initials: G
authors.lastname: Grandi
mesh_terms: D000818:Animals; D000907:Antibodies, Bacterial / Q000235:genetics / Q000276:immunology; D000942:Antigens, Bacterial / Q000145:classification / Q000235:genetics / Q000276:immunology; D001428:Bacterial Vaccines / Q000235:genetics* / Q000276:immunology*; D001980:Bronchi / Q000276:immunology; D002460:Cell Line; D004847:Epithelial Cells / Q000276:immunology; D015964:Gene Expression Regulation, Bacterial; D016680:Genome, Bacterial; D006801:Humans; D051379:Mice; D038541:Neisseria meningitidis, Serogroup B / Q000235:genetics* / Q000276:immunology*; D020411:Oligonucleotide Array Sequence Analysis / Q000295:instrumentation / Q000379:methods*; D020539:Sequence Analysis, Protein
chemical_list: D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001428:Bacterial Vaccines