Neisseria meningitidis is a human pathogen, which, in spite of antibiotic therapy, is still a major cause of mortality due to sepsis and meningitis. Here we describe NadA, a novel surface antigen of N. meningitidis that is present in 52 out of 53 strains of hypervirulent lineages electrophoretic types (ET) ET37, ET5, and cluster A4. The gene is absent in the hypervirulent lineage III, in N. gonorrhoeae and in the commensal species N. lactamica and N. cinerea. The guanine/cytosine content, lower than the chromosome, suggests acquisition by horizontal gene transfer and subsequent limited evolution to generate three well-conserved alleles. NadA has a predicted molecular structure strikingly similar to a novel class of adhesins (YadA and UspA2), forms high molecular weight oligomers, and binds to epithelial cells in vitro supporting the hypothesis that NadA is important for host cell interaction. NadA induces strong bactericidal antibodies and is protective in the infant rat model suggesting that this protein may represent a novel antigen for a vaccine able to control meningococcal disease caused by three hypervirulent lineages.
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3 June 2002
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May 28 2002
NadA, a Novel Vaccine Candidate of Neisseria meningitidis
Maurizio Comanducci,
Maurizio Comanducci
1Immunological Research Institute Siena, Chiron S.p.A., 53100 Siena, Italy
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Stefania Bambini,
Stefania Bambini
1Immunological Research Institute Siena, Chiron S.p.A., 53100 Siena, Italy
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Brunella Brunelli,
Brunella Brunelli
1Immunological Research Institute Siena, Chiron S.p.A., 53100 Siena, Italy
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Jeannette Adu-Bobie,
Jeannette Adu-Bobie
1Immunological Research Institute Siena, Chiron S.p.A., 53100 Siena, Italy
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Beatrice Aricò,
Beatrice Aricò
1Immunological Research Institute Siena, Chiron S.p.A., 53100 Siena, Italy
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Barbara Capecchi,
Barbara Capecchi
1Immunological Research Institute Siena, Chiron S.p.A., 53100 Siena, Italy
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Marzia Monica Giuliani,
Marzia Monica Giuliani
1Immunological Research Institute Siena, Chiron S.p.A., 53100 Siena, Italy
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Vega Masignani,
Vega Masignani
1Immunological Research Institute Siena, Chiron S.p.A., 53100 Siena, Italy
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Laura Santini,
Laura Santini
1Immunological Research Institute Siena, Chiron S.p.A., 53100 Siena, Italy
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Silvana Savino,
Silvana Savino
1Immunological Research Institute Siena, Chiron S.p.A., 53100 Siena, Italy
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Dan M. Granoff,
Dan M. Granoff
2Children's Hospital Oakland Research Institute, Oakland, CA 94609
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Dominique A. Caugant,
Dominique A. Caugant
3WHO Collaborating Centre for Reference and Research on Meningococci, National Institute of Public Health, N-0403 Oslo, Norway
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Mariagrazia Pizza,
Mariagrazia Pizza
1Immunological Research Institute Siena, Chiron S.p.A., 53100 Siena, Italy
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Rino Rappuoli,
Rino Rappuoli
1Immunological Research Institute Siena, Chiron S.p.A., 53100 Siena, Italy
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Marirosa Mora
Marirosa Mora
1Immunological Research Institute Siena, Chiron S.p.A., 53100 Siena, Italy
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Maurizio Comanducci
1Immunological Research Institute Siena, Chiron S.p.A., 53100 Siena, Italy
Stefania Bambini
1Immunological Research Institute Siena, Chiron S.p.A., 53100 Siena, Italy
Brunella Brunelli
1Immunological Research Institute Siena, Chiron S.p.A., 53100 Siena, Italy
Jeannette Adu-Bobie
1Immunological Research Institute Siena, Chiron S.p.A., 53100 Siena, Italy
Beatrice Aricò
1Immunological Research Institute Siena, Chiron S.p.A., 53100 Siena, Italy
Barbara Capecchi
1Immunological Research Institute Siena, Chiron S.p.A., 53100 Siena, Italy
Marzia Monica Giuliani
1Immunological Research Institute Siena, Chiron S.p.A., 53100 Siena, Italy
Vega Masignani
1Immunological Research Institute Siena, Chiron S.p.A., 53100 Siena, Italy
Laura Santini
1Immunological Research Institute Siena, Chiron S.p.A., 53100 Siena, Italy
Silvana Savino
1Immunological Research Institute Siena, Chiron S.p.A., 53100 Siena, Italy
Dan M. Granoff
2Children's Hospital Oakland Research Institute, Oakland, CA 94609
Dominique A. Caugant
3WHO Collaborating Centre for Reference and Research on Meningococci, National Institute of Public Health, N-0403 Oslo, Norway
Mariagrazia Pizza
1Immunological Research Institute Siena, Chiron S.p.A., 53100 Siena, Italy
Rino Rappuoli
1Immunological Research Institute Siena, Chiron S.p.A., 53100 Siena, Italy
Marirosa Mora
1Immunological Research Institute Siena, Chiron S.p.A., 53100 Siena, Italy
Address correspondence to Rino Rappuoli, IRIS, Chiron S.p.A., via Fiorentina 1, 53100 Siena, Italy. Phone: 39-0577-243414; Fax: 39-0577-278508; E-mail: [email protected]
The online version of this paper contains supplemental material.
*
Abbreviations used in this paper: ET, electrophoretic type; GC, gonococcus; MenB, serogroup B N. meningitidis; ORF, open reading frame; ST, sequence type.
Received:
March 13 2002
Revision Received:
April 03 2002
Accepted:
April 16 2002
Online ISSN: 1540-9538
Print ISSN: 0022-1007
The Rockefeller University Press
2002
J Exp Med (2002) 195 (11): 1445–1454.
Article history
Received:
March 13 2002
Revision Received:
April 03 2002
Accepted:
April 16 2002
Citation
Maurizio Comanducci, Stefania Bambini, Brunella Brunelli, Jeannette Adu-Bobie, Beatrice Aricò, Barbara Capecchi, Marzia Monica Giuliani, Vega Masignani, Laura Santini, Silvana Savino, Dan M. Granoff, Dominique A. Caugant, Mariagrazia Pizza, Rino Rappuoli, Marirosa Mora; NadA, a Novel Vaccine Candidate of Neisseria meningitidis . J Exp Med 3 June 2002; 195 (11): 1445–1454. doi: https://doi.org/10.1084/jem.20020407
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