Wedege E, Kolberg J, Delvig A, Høiby E A, Holten E, Rosenqvist E, Caugant D A
Department of Vaccine, National Institute of Public Health, Oslo, Norway.
Clin Diagn Lab Immunol. 1995 May;2(3):314-21. doi: 10.1128/cdli.2.3.314-321.1995.
An increase in B:15:P1.12 meningococci among isolates from patients with Neisseria meningitidis infection in Norway in recent years led to further characterization of such strains. Between 1987 and 1992, B:15:P1.12 strains constituted 9.8% (24 strains) of B:15 isolates. The B:15:P1.12 strains belonged to the electrophoretic type 5 (ET-5) complex, but 17 (71%) strains were a new clone (ET-5c) not found elsewhere in the world. All but one strain of ET-5c were responsible for a localized outbreak of systemic meningococcal disease in western Norway. A novel monoclonal antibody (202,G-12), developed against the unknown variable region 2 on the class 1 protein of one of these strains, bound to 19 of the 15:P1.12 strains, 4 strains bound the subtype P1.13 reference monoclonal antibody MN24H10.75, and the remaining strain showed no reaction. Sequencing of porA genes demonstrated a series of nine threonine residues in the deduced variable region 2 of the latter strain, while four and five threonine residues were found in the corresponding regions of strains reacting with the monoclonal antibodies 202,G-12 and MN24H10.75, respectively. Epitope mapping with synthetic peptides showed that 202,G-12 bound to a sequence of 11 amino acids which included the four threonine residues specific for subtype P1.13a. Immunoglobulin G antibodies against the P1.7,16 subtype protein, induced in volunteers after vaccination with the Norwegian meningococcal vaccine, did not cross-react on immunoblots with the subtype protein of clone ET-5c. Thus, postvaccination class 1 protein antibodies, assumed to be protective, may not be effective against infection with the new clone.
近年来,挪威脑膜炎奈瑟菌感染患者分离株中B:15:P1.12脑膜炎球菌数量增加,促使对这类菌株进行进一步特性分析。1987年至1992年间,B:15:P1.12菌株占B:15分离株的9.8%(24株)。B:15:P1.12菌株属于电泳型5(ET-5)复合体,但17株(71%)是世界其他地方未发现的新克隆株(ET-5c)。除1株外,所有ET-5c菌株均导致挪威西部局部爆发全身性脑膜炎球菌病。针对其中一株菌株1类蛋白上未知可变区2开发的一种新型单克隆抗体(202,G-12),与15:P1.12菌株中的19株结合,4株与亚型P1.13参考单克隆抗体MN24H10.75结合,其余菌株无反应。对porA基因进行测序发现,后一株菌株推导的可变区2中有一系列9个苏氨酸残基,而与单克隆抗体202,G-12和MN24H10.75反应的菌株相应区域分别发现4个和5个苏氨酸残基。用合成肽进行表位作图表明,202,G-12与一段包含P1.13a亚型特有的4个苏氨酸残基的11个氨基酸序列结合。志愿者接种挪威脑膜炎球菌疫苗后诱导产生的针对P1.7,16亚型蛋白的免疫球蛋白G抗体,在免疫印迹上与克隆ET-5c的亚型蛋白无交叉反应。因此,假定具有保护作用的疫苗接种后1类蛋白抗体可能对新克隆株感染无效。