Saunders N B, Brandt B L, Warren R L, Hansen B D, Zollinger W D
Department of Bacterial Diseases, Walter Reed Army Institute of Research, Washington, DC 20307-5100, USA.
Infect Immun. 1998 Jul;66(7):3218-22. doi: 10.1128/IAI.66.7.3218-3222.1998.
Epidemic outbreaks of group B meningococcal disease exhibit a clonal nature consisting of a common serotype-subtype. Subtype-specific monoclonal antibodies (MAbs) directed toward two variable regions (VR1 and VR2) of the class 1 protein of Neisseria meningitidis are used in this classification scheme. A new MAb was developed to classify a nonsubtypeable (NST) strain of N. meningitidis, 7967. This MAb bound to both the NST strain and the prototype subtype P1. 14 strain, S3446, by dot blot analysis. However, a MAb produced to the prototype P1.14 strain did not bind to strain 7967. Sixteen additional strains were further identified as P1.14 with the prototype MAb; of these, 15 strains bound both MAbs. Differences in the characteristics of binding of both antibodies to the three apparently diverse P1.14 strains were studied further by using outer membrane complex proteins, immobilized peptides, and soluble peptides. Deduced amino acid analysis suggested that both MAbs bind to VR2 and that single amino acid changes within VR2 (KM, NM, or KK) might explain the differences in binding characteristics. These results demonstrated that minor variations which exist within subtype variable regions may be clearly identified only by a combination of molecular and immunologic testing. The impact of subtype variation will become more evident as subtype-specific vaccines are developed and tested for efficacy.
B 群脑膜炎球菌病的流行暴发呈现出由一种常见血清型 - 亚型组成的克隆性质。针对脑膜炎奈瑟菌 1 类蛋白的两个可变区(VR1 和 VR2)的亚型特异性单克隆抗体(MAb)用于此分类方案。开发了一种新的单克隆抗体来对一株不可分型(NST)的脑膜炎奈瑟菌 7967 进行分型。通过斑点印迹分析,该单克隆抗体与 NST 菌株以及原型亚型 P1.14 菌株 S3446 均结合。然而,针对原型 P1.14 菌株产生的单克隆抗体不与菌株 7967 结合。另外 16 株菌株通过原型单克隆抗体被进一步鉴定为 P1.14;其中,15 株菌株与两种单克隆抗体均结合。通过使用外膜复合蛋白、固定化肽和可溶性肽,进一步研究了两种抗体与三种明显不同的 P1.14 菌株结合特性的差异。推导的氨基酸分析表明,两种单克隆抗体均与 VR2 结合,并且 VR2 内的单个氨基酸变化(KM、NM 或 KK)可能解释了结合特性的差异。这些结果表明,仅通过分子和免疫检测相结合才能清楚地识别亚型可变区内存在的微小变异。随着亚型特异性疫苗的开发和疗效测试,亚型变异的影响将变得更加明显。