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NadA, a Novel Vaccine Candidate of Neisseria meningitidis

Maurizio Comanducci¹, Stefania Bambini¹, Brunella Brunelli¹, Jeannette Adu-Bobie¹, Beatrice Aricò¹, Barbara Capecchi¹, Marzia Monica Giuliani¹, Vega Masignani¹, Laura Santini¹, Silvana Savino¹, Dan M. Granoff², Dominique A. Caugant³, Mariagrazia Pizza¹, Rino Rappuoli¹ and Marirosa Mora¹

¹ Immunological Research Institute Siena, Chiron S.p.A., 53100 Siena, Italy
² Children's Hospital Oakland Research Institute, Oakland, CA 94609
³ WHO Collaborating Centre for Reference and Research on Meningococci, National Institute of Public Health, N-0403 Oslo, Norway

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: rino_rappuoli{at}chiron.it

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.

Key Words: N. meningitidis • meningococcus • adhesin • pathogenesis • vaccine

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