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去N-乙酰化唾液酸具有免疫原性,能引发针对脑膜炎奈瑟菌的保护性抗体。

De-N-acetylated sialic acid is immunogenic and elicits antibodies that are protective against Neisseria meningitidis.

作者信息

Moe Gregory R, Flitter Becca A, Ing Jessica Y, Bhandari Tamara S, Kaur Hardeep

机构信息

Center for Immunobiology and Vaccine Development, Children's Hospital & Research Center Oakland, Oakland, CA 94609.

出版信息

Vaccimonitor. 2009;18(2):61-65.

Abstract

Recently, we showed that monoclonal antibodies (mAbs) that are reactive with derivatives of polysialic acid containing de-N-acetylated neuraminic acid (Neu) residues are protective against N. meningitidis group B strains (Moe et al. 2005, Infect Immun73: 2123; Flitter et al., in preparation). In addition, we found that fully de-N-acetylated PSA (i.e. poly alpha 2,8 Neu) conjugated to tetanus toxoid (DeNAc) elicits IgM and IgG antibodies of all subclasses in mice that bind to group B strains, activate human complement deposition, are protective in an infant rat model of meningococcal bacteremia and are bactericidal against group C strains (Moe et al, in press). We show here that anti-DeNAc mAbs, DA1 and DA2 (both IgM), are reactive with polysaccharides containing Neu, bind to group B, C, W135 and Y but not X strains grown in chemically defined media (CDM). However, when the group X strain is grown in CDM supplemented with human plasma, DA2 binds. Also both mAbs mediate bactericidal activity against B, C, W135, and X strains with human complement. The results suggests that N. meningitidis express and/or acquire zwitterionic de-N-acetyl sialic acid antigens that can be the target of protective antibodies.

摘要

最近,我们发现与含有去N-乙酰化神经氨酸(Neu)残基的聚唾液酸衍生物反应的单克隆抗体(mAbs)对B群脑膜炎奈瑟菌菌株具有保护作用(Moe等人,2005年,《感染与免疫》73: 2123;Flitter等人,正在准备中)。此外,我们发现与破伤风类毒素偶联的完全去N-乙酰化的PSA(即聚α2,8 Neu)(DeNAc)在小鼠中引发所有亚类的IgM和IgG抗体,这些抗体可结合B群菌株,激活人补体沉积,在婴儿大鼠脑膜炎球菌血症模型中具有保护作用,并且对C群菌株具有杀菌作用(Moe等人,即将发表)。我们在此表明,抗DeNAc单克隆抗体DA1和DA2(均为IgM)与含有Neu的多糖反应,可结合在化学成分确定的培养基(CDM)中生长的B、C、W135和Y群菌株,但不结合X群菌株。然而,当X群菌株在补充有人血浆的CDM中生长时,DA2会结合。此外,这两种单克隆抗体均可介导对B、C、W135和X群菌株的人补体杀菌活性。结果表明,脑膜炎奈瑟菌表达和/或获得两性离子去N-乙酰化唾液酸抗原,这些抗原可以成为保护性抗体的靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4dc4/3149888/ff052e9995d3/nihms280816f1.jpg

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