4.7 Article

NadA, a novel vaccine candidate of Neisseria meningitidis

Journal

JOURNAL OF EXPERIMENTAL MEDICINE
Volume 195, Issue 11, Pages 1445-1454

Publisher

ROCKEFELLER UNIV PRESS
DOI: 10.1084/jem.20020407

Keywords

N. meningitidis; meningococcus; adhesin; pathogenesis; vaccine

Funding

  1. NIAID NIH HHS [R01 AI 45642, R01 AI046464, R01 AI045642, AI 46464] Funding Source: Medline
  2. Wellcome Trust Funding Source: Medline

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Neisscria 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. gouorrhoeac and in the commensal species N. lactamica and N. cinerea. The guainne/cytosine content, lower than the chromosome, suggests acquisition by horizontal gene transfer and subsequent limited evolution to generate three Nvell-conserved alleles. NadA has a predicted molecular structure strikingly similar to a novel class of adhesins (YadA and UspA2), fornis high molecular weight oligoiners, 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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