NadA, a novel vaccine candidate of Neisseria meningitidis

被引:292
作者
Comanducci, M
Bambini, S
Brunelli, B
Adu-Bobie, J
Aricò, B
Capecchi, B
Giuliani, MM
Masignani, V
Santini, L
Savino, S
Granoff, DM
Caugant, DA
Pizza, M
Rappuoli, R
Mora, M
机构
[1] Immunol Res Inst Siena, Chiron SpA, I-53100 Siena, Italy
[2] Childrens Hosp, Oakland Res Inst, Oakland, CA 94609 USA
[3] Natl Inst Publ Hlth, WHO, Collaborating Ctr Reference & Res Meningococci, N-0403 Oslo, Norway
基金
英国惠康基金;
关键词
N; meningitidis; meningococcus; adhesin; pathogenesis; vaccine;
D O I
10.1084/jem.20020407
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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.
引用
收藏
页码:1445 / 1454
页数:10
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