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Previously unrecognized vaccine candidates against group B meningococcus identified by DNA microarrays

Nature Biotechnology volume 20, pages 914–921 (2002)Cite this article

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.

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Figure 1: Kinetics of adhesion, growth, and gene expression in MenB.
Figure 2: Remodeling of surface-associated antigens in epithelial cell–adhering bacteria.
Figure 3: FACS analysis of MC58 gene deletion mutants.
Figure 4: Schematic representation of amino-acid sequence variability within N. meningitidis of the five antigens reported in Table 3.

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Acknowledgements

We thank J. Telford for the critical reading of the manuscript and R. Moxon and D.A. Caugant for providing bacterial strains. We also thank M. Comanducci for providing genomic DNAs, V. Masignani, M. Scarselli, and R. Beltrami for assistance in computer analysis, S. Censini and S. Guidotti for nucleotide sequencing, G. Corsi for artwork, and A. Maiorino for expert secretarial assistance.

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Authors and Affiliations

  1. Chiron SpA, Via Fiorentina 1, Siena, 53100, Italy

    Renata Grifantini, Erika Bartolini, Alessandro Muzzi, Monia Draghi, Elisabetta Frigimelica, Giulio Ratti, Roberto Petracca, Giuliano Galli, Mauro Agnusdei, Marzia Monica Giuliani, Laura Santini, Brunella Brunelli, Rino Rappuoli & Guido Grandi

  2. Chiron Corporation, 4560 Horton Street, Emeryville, 94608, CA

    Joel Berger & Filippo Randazzo

  3. The Institute for Genomic Research (TIGR), 9712 Medical Center Drive, Rockville, 20850, MD

    Hervé Tettelin

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Correspondence to Guido Grandi.

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Grifantini, R., Bartolini, E., Muzzi, A. et al. Previously unrecognized vaccine candidates against group B meningococcus identified by DNA microarrays. Nat Biotechnol 20, 914–921 (2002). https://doi.org/10.1038/nbt728

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