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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 Rappuoli1
Neisseria meningitidis is a major cause of
bacterial septicemia and meningitis. Sequence variation of
surface-exposed proteinsand cross-reactivity of the serogroup B
capsular polysaccharidewith human tissues have hampered efforts to
develop a successfulvaccine. To overcome these obstacles, the entire
genome sequenceof a virulent serogroup B strain (MC58) was used to
identify vaccinecandidates. A total of 350 candidate antigens were
expressed inEscherichia coli, purified, and used to
immunize mice. The seraallowed the identification of proteins that are
surface exposed,that are conserved in sequence across a range of
strains, andthat induce a bactericidal antibody response, a property
knownto 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.
To whom correspondence should be addressed. E-mail:
Rino_Rappuoli{at}biocine.it
The editors suggest the following Related Resources on Science sites:
In Science Magazine
PERSPECTIVES
Xavier Nassif (10 March 2000) Science287 (5459), 1767.
[DOI: 10.1126/science.287.5459.1767] |Summary »|Full Text »
REPORTS
Hervé Tettelin, Nigel J. Saunders, John Heidelberg, Alex C. Jeffries, Karen E. Nelson, Jonathan A. Eisen, Karen A. Ketchum, Derek W. Hood, John F. Peden, Robert J. Dodson, William C. Nelson, Michelle L. Gwinn, Robert DeBoy, Jeremy D. Peterson, Erin K. Hickey, Daniel H. Haft, Steven L. Salzberg, Owen White, Robert D. Fleischmann, Brian A. Dougherty, Tanya Mason, Anne Ciecko, Debbie S. Parksey, Eric Blair, Henry Cittone, Emily B. Clark, Matthew D. Cotton, Terry R. Utterback, Hoda Khouri, Haiying Qin, Jessica Vamathevan, John Gill, Vincenzo Scarlato, Vega Masignani, Mariagrazia Pizza, Guido Grandi, Li Sun, Hamilton O. Smith, Claire M. Fraser, E. Richard Moxon, Rino Rappuoli, and J. Craig Venter (10 March 2000) Science287 (5459), 1809.
[DOI: 10.1126/science.287.5459.1809] |Abstract »|Full Text »|PDF »
