Previously unrecognized vaccine candidates against group B meningococcus identified by DNA microarrays.
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.
Grifantini
Renata
R
Chiron SpA, Via Fiorentina 1, 53100 Siena, Italy.
Bartolini
Erika
E
Muzzi
Alessandro
A
Draghi
Monia
M
Frigimelica
Elisabetta
E
Berger
Joel
J
Ratti
Giulio
G
Petracca
Roberto
R
Galli
Giuliano
G
Agnusdei
Mauro
M
Giuliani
Marzia Monica
MM
Santini
Laura
L
Brunelli
Brunella
B
Tettelin
Hervé
H
Rappuoli
Rino
R
Randazzo
Filippo
F
Grandi
Guido
G
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
D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001428:Bacterial Vaccines