Identification of Vaccine Candidates Against Serogroup B Meningococcus by Whole-Genome Sequencing

Author:

Pizza Mariagrazia1,Scarlato Vincenzo1,Masignani Vega1,Giuliani Marzia Monica1,Aricò Beatrice1,Comanducci Maurizio1,Jennings Gary T.1,Baldi Lucia1,Bartolini Erika1,Capecchi Barbara1,Galeotti Cesira L.1,Luzzi Enrico1,Manetti Roberto1,Marchetti Elisa1,Mora Marirosa1,Nuti Sandra1,Ratti Giulio1,Santini Laura1,Savino Silvana1,Scarselli Maria1,Storni Elisa1,Zuo Peijun1,Broeker Michael2,Hundt Erika2,Knapp Bernard2,Blair Eric3,Mason Tanya3,Tettelin Hervé3,Hood Derek W.4,Jeffries Alex C.4,Saunders Nigel J.4,Granoff Dan M.5,Venter J. Craig3,Moxon E. Richard4,Grandi Guido1,Rappuoli Rino1

Affiliation:

1. IRIS, Chiron S.p.A., Via Fiorentina 1, 53100 Siena, Italy.

2. Chiron Behring, Post Office Box 1630, D-35006 Marburg, Germany.

3. The Institute for Genomic Research, 9712 Medical Center Drive, Rockville, MD 20850, USA.

4. Institute of Molecular Medicine, Oxford University, Department of Paediatrics, John Radcliffe Hospital, Headington, Oxford OX3 9DS, UK.

5. Children's Hospital Oakland Research Institute, 5700 Martin Luther King Jr. Way, Oakland, CA 94609, USA.

Abstract

Neisseria meningitidis is a major cause of bacterial septicemia and meningitis . Sequence variation of surface-exposed proteins and cross-reactivity of the serogroup B capsular polysaccharide with human tissues have hampered efforts to develop a successful vaccine. To overcome these obstacles, the entire genome sequence of a virulent serogroup B strain (MC58) was used to identify vaccine candidates. A total of 350 candidate antigens were expressed in Escherichia coli , purified, and used to immunize mice. The sera allowed the identification of proteins that are surface exposed, that are conserved in sequence across a range of strains, and that induce a bactericidal antibody response, a property known to correlate with vaccine efficacy in humans.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

Reference59 articles.

1. HUMAN IMMUNITY TO THE MENINGOCOCCUS

2. HUMAN IMMUNITY TO THE MENINGOCOCCUS

3. W. D. Zollinger in New Generation Vaccines M. M. Levine G. C. Woodrow J. B. Kaper G. S. Cobon Eds. (Dekker New York 1997) p. 469

4. H. Peltola Drugs 55 (no. 3) 347 (1998).

5. Schuchat A., et al., N. Engl. J. Med. 337, 970 (1997).

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