Wedege Elisabeth, Kuipers Betsy, Bolstad Karin, van Dijken Harry, Frøholm L Oddvar, Vermont Clementien, Caugant Dominique A, van den Dobbelsteen Germie
Division of Infectious Disease Control, Norwegian Institute of Public Health, N-0403 Oslo, Norway.
Infect Immun. 2003 Jul;71(7):3775-81. doi: 10.1128/IAI.71.7.3775-3781.2003.
Antibody specificities of pre- and postvaccination serum samples from 40 (53%) teenagers who received three doses of the Norwegian Neisseria meningitidis serogroup B vaccine (B:15:P1.7,16) during a previous trial in Iceland (Perkins et al., J. Infect. Dis. 177:683-691, 1998) were analyzed with serum bactericidal activity (SBA) and immunoblotting assays with reference and isogenic meningococcal H44/76 vaccine strains. The H44/76 variants demonstrated significant vaccine-induced SBA to P1.7,16 PorA and Opc but not to PorB, Opa5.5, and a heterologous PorA protein. On blots, immunoglobulin G levels to all these proteins increased significantly after vaccination. Measurement of SBA to the two main variable regions (P1.7 and P1.16) on the P1.7,16 PorA with PorA deletion mutants revealed significantly higher activity to the P1.7,- and P1.-,16 mutants compared to the P1.7,16 strain, indicating exposure of new accessible epitopes. Only 12 (30%) serum samples showed distinct decreases with these or the P1.-,- mutant, with most samples containing SBA to the P1.7 and P1.16 combination. In contrast, P1.16-specific antibodies were mainly found on blots. Thirteen of the vaccinees (32.5%) were carriers of meningococci at the time of the third dose, of whom four (30.8%) harbored strains of the ET-5 complex. Carriage of P1.15 strains was generally reflected in > or =4-fold increases in SBA and distinct immunoglobulin G binding to the P1.19,15 PorA on blots. Although vaccination did not elicit bactericidal activity to the serotype 15 PorB, most carriers of serotype 15 strains showed > or =4-fold increases in SBA to this antigen.
在冰岛之前的一项试验中(Perkins等人,《传染病杂志》177:683 - 691,1998年),对40名(53%)青少年接种三剂挪威B群脑膜炎奈瑟菌疫苗(B:15:P1.7,16)前后血清样本的抗体特异性进行了分析,采用血清杀菌活性(SBA)以及针对参考和同基因脑膜炎球菌H44/76疫苗菌株的免疫印迹分析。H44/76变体显示出疫苗诱导的针对P1.7,16 PorA和Opc的显著SBA,但对PorB、Opa5.5和一种异源PorA蛋白则无此活性。在印迹上,接种疫苗后针对所有这些蛋白的免疫球蛋白G水平显著升高。用PorA缺失突变体对P1.7,16 PorA上的两个主要可变区(P1.7和P1.16)进行SBA测量,结果显示与P1.7,16菌株相比,针对P1.7 - 和P1. - ,16突变体的活性显著更高,表明有新的可及表位暴露。只有12份(30%)血清样本对这些或P1. - , - 突变体显示出明显降低,大多数样本含有针对P1.7和P1.16组合的SBA。相比之下,P1.16特异性抗体主要在印迹上被发现。13名(32.5%)疫苗接种者在接种第三剂时是脑膜炎球菌携带者,其中4名(30.8%)携带ET - 5复合体菌株。携带P1.15菌株通常表现为SBA升高≥4倍,且在印迹上针对P1.19,15 PorA有明显的免疫球蛋白G结合。尽管接种疫苗未引发针对15型PorB的杀菌活性,但大多数15型菌株携带者针对该抗原的SBA升高≥4倍。