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Science 10 March 2000:
Vol. 287. no. 5459, pp. 1816 - 1820
DOI: 10.1126/science.287.5459.1816
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Reports

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

Mariagrazia Pizza, 1* Vincenzo Scarlato, 1* Vega Masignani, 1 Marzia Monica Giuliani, 1 Beatrice Aricò, 1 Maurizio Comanducci, 1 Gary T. Jennings, 1 Lucia Baldi, 1 Erika Bartolini, 1 Barbara Capecchi, 1 Cesira L. Galeotti, 1 Enrico Luzzi, 1 Roberto Manetti, 1 Elisa Marchetti, 1 Marirosa Mora, 1 Sandra Nuti, 1 Giulio Ratti, 1 Laura Santini, 1 Silvana Savino, 1 Maria Scarselli, 1 Elisa Storni, 1 Peijun Zuo, 1 Michael Broeker, 2 Erika Hundt, 2 Bernard Knapp, 2 Eric Blair, 3 Tanya Mason, 3 Hervé Tettelin, 3 Derek W. Hood, 4 Alex C. Jeffries, 4 Nigel J. Saunders, 4 Dan M. Granoff, 5 J. Craig Venter, 3 E. Richard Moxon, 4 Guido Grandi, 1 Rino Rappuoli 1dagger

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.

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.
*   These authors contributed equally to this work.

dagger    To whom correspondence should be addressed. E-mail: Rino_Rappuoli{at}biocine.it

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Interactions among Strategies Associated with Bacterial Infection: Pathogenicity, Epidemicity, and Antibiotic Resistance.
J. L. Martinez and F. Baquero (2002)
Clin. Microbiol. Rev. 15, 647-679
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Factors Influencing the Identification of Transcription Factor Binding Sites by Cross-Species Comparison.
L. A. McCue, W. Thompson, C. S. Carmack, and C. E. Lawrence (2002)
Genome Res. 12, 1523-1532
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Complete genome sequence and comparative genomic analysis of an emerging human pathogen, serotype V Streptococcus agalactiae.
H. Tettelin, V. Masignani, M. J. Cieslewicz, J. A. Eisen, S. Peterson, M. R. Wessels, I. T. Paulsen, K. E. Nelson, I. Margarit, T. D. Read, et al. (2002)
PNAS 99, 12391-12396
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Enhancement of Protective Efficacy following Intranasal Immunization with Vaccine Plus a Nontoxic LTK63 Mutant Delivered with Nanoparticles.
B. C. Baudner, O. Balland, M. M. Giuliani, P. Von Hoegen, R. Rappuoli, D. Betbeder, and G. Del Giudice (2002)
Infect. Immun. 70, 4785-4790
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Overview of vaccines and immunisation.
M. M Levine, J. D Campbell, and K. L Kotloff (2002)
Br. Med. Bull. 62, 1-13
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Bacterial pathogen genomics and vaccines.
R. Moxon and R. Rappuoli (2002)
Br. Med. Bull. 62, 45-58
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Vaccines against dangerous pathogens.
E D Williamson and R W Titball (2002)
Br. Med. Bull. 62, 163-173
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The meningococcus tamed?.
A J Pollard and E R Moxon (2002)
Arch. Dis. Child. 87, 13-17
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NadA, a Novel Vaccine Candidate of Neisseria meningitidis.
M. Comanducci, S. Bambini, B. Brunelli, J. Adu-Bobie, B. Arico, B. Capecchi, M. M. Giuliani, V. Masignani, L. Santini, S. Savino, et al. (2002)
J. Exp. Med. 195, 1445-1454
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Identification of in vivo expressed vaccine candidate antigens from Staphylococcus aureus.
H. Etz, D. B. Minh, T. Henics, A. Dryla, B. Winkler, C. Triska, A. P. Boyd, J. Sollner, W. Schmidt, U. von Ahsen, et al. (2002)
PNAS 99, 6573-6578
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Genomic Approach for Analysis of Surface Proteins in Chlamydia pneumoniae.
S. Montigiani, F. Falugi, M. Scarselli, O. Finco, R. Petracca, G. Galli, M. Mariani, R. Manetti, M. Agnusdei, R. Cevenini, et al. (2002)
Infect. Immun. 70, 368-379
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Identification, Characterization, and Variable Expression of a Naturally Occurring Inhibitor Protein of IS1106 Transposase in Clinical Isolates of Neisseriameningitidis.
P. Salvatore, C. Pagliarulo, R. Colicchio, P. Zecca, G. Cantalupo, M. Tredici, A. Lavitola, C. Bucci, C. B. Bruni, and P. Alifano (2001)
Infect. Immun. 69, 7425-7436
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A Novel Mimetic Antigen Eliciting Protective Antibody to Neisseria meningitidis.
D. M. Granoff, G. R. Moe, M. M. Giuliani, J. Adu-Bobie, L. Santini, B. Brunelli, F. Piccinetti, P. Zuno-Mitchell, S. S. Lee, P. Neri, et al. (2001)
J. Immunol. 167, 6487-6496
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Pneumococcal Research Transformed.
J. M. Musser and S. L. Kaplan (2001)
N. Engl. J. Med. 345, 1206-1207
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Multilocus analysis of extracellular putative virulence proteins made by group A Streptococcus: Population genetics, human serologic response, and gene transcription.
S. D. Reid, N. M. Green, J. K. Buss, B. Lei, and J. M. Musser (2001)
PNAS 98, 7552-7557
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Functional Activity of Anti-Neisserial Surface Protein A Monoclonal Antibodies against Strains of Neisseria meningitidis Serogroup B.
G. R. Moe, P. Zuno-Mitchell, S. S. Lee, A. H. Lucas, and D. M. Granoff (2001)
Infect. Immun. 69, 3762-3771
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Improved Pattern for Genome-Based Screening Identifies Novel Cell Wall-Attached Proteins in Gram-Positive Bacteria.
R. Janulczyk and M. Rasmussen (2001)
Infect. Immun. 69, 4019-4026
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Meningococcal Disease.
N. E. Rosenstein, B. A. Perkins, D. S. Stephens, T. Popovic, and J. M. Hughes (2001)
N. Engl. J. Med. 344, 1378-1388
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Monoclonal Antibodies Specific for Neisseria meningitidis Group B Polysaccharide and Their Peptide Mimotopes.
J. S. Shin, J. S. Lin, P. W. Anderson, R. A. Insel, and M. H. Nahm (2001)
Infect. Immun. 69, 3335-3342
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Neisserial TonB-dependent outer-membrane proteins: detection, regulation and distribution of three putative candidates identified from the genome sequences.
P. C. Turner, C. E. Thomas, I. Stojiljkovic, C. Elkins, G. Kizel, D. A. A. Ala’Aldeen, and P. F. Sparling (2001)
Microbiology 147, 1277-1290
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