Moe Gregory R, Flitter Becca A, Ing Jessica Y, Bhandari Tamara S, Kaur Hardeep
Center for Immunobiology and Vaccine Development, Children's Hospital & Research Center Oakland, Oakland, CA 94609.
Vaccimonitor. 2009;18(2):61-65.
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.
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。