Norheim Gunnstein, Aseffa Abraham, Yassin Mohammed Ahmed, Mengistu Getahun, Kassu Afework, Fikremariam Dereje, Tamire Wegene, Merid Yared, Høiby E Arne, Caugant Dominique A, Fritzsønn Elisabeth, Tangen Torill, Melak Berhanu, Berhanu Degu, Harboe Morten, Kolberg Jan, Rosenqvist Einar
Division of Infectious Disease Control, Norwegian Institute of Public Health, Oslo, Norway.
Clin Vaccine Immunol. 2008 May;15(5):863-71. doi: 10.1128/CVI.00252-07. Epub 2008 Mar 12.
Dissecting the specificities of human antibody responses following disease caused by serogroup A meningococci may be important for the development of improved vaccines. We performed a study of Ethiopian patients during outbreaks in 2002 and 2003. Sera were obtained from 71 patients with meningitis caused by bacteria of sequence type 7, as confirmed by PCR or culture, and from 113 Ethiopian controls. Antibody specificities were analyzed by immunoblotting (IB) against outer membrane antigen extracts of a reference strain and of the patients' own isolates and by enzyme-linked immunosorbent assay for immunoglobulin G (IgG) levels against lipooligosaccharide (LOS) L11 and the proteins NadA and NspA. IB revealed that the main antigens targeted were the proteins PorA, PorB, RmpM, and Opa/OpcA, as well as LOS. MenA disease induced significant increases in IgG against LOS L11 and NadA. The IgG levels against LOS remained elevated following disease, whereas the IgG anti-NadA levels returned to acute-phase levels in the late convalescent phase. Among adults, the anti-LOS IgG levels were similar in acute-phase patient sera as in control sera, whereas anti-NadA IgG levels were significantly higher in acute-phase sera than in controls. The IgG antibody levels against LOS and NadA correlated moderately but significantly with serum bactericidal activity against MenA strains. Future studies on immune response during MenA disease should take into account the high levels of anti-MenA polysaccharide IgG commonly found in the population and seek to clarify the role of antibodies against subcapsular antigens in protection against MenA disease.
剖析A群脑膜炎球菌所致疾病后人类抗体反应的特异性,可能对研发改良疫苗具有重要意义。我们于2002年和2003年疫情期间对埃塞俄比亚患者进行了一项研究。通过PCR或培养确诊,从71例由序列型7细菌引起脑膜炎的患者以及113名埃塞俄比亚对照者中获取血清。通过针对参考菌株和患者自身分离株的外膜抗原提取物进行免疫印迹(IB),以及通过酶联免疫吸附测定法检测针对脂寡糖(LOS)L11、蛋白NadA和NspA的免疫球蛋白G(IgG)水平,来分析抗体特异性。免疫印迹显示,主要靶向抗原为蛋白PorA、PorB、RmpM和Opa/OpcA以及LOS。A群脑膜炎球菌病导致针对LOS L11和NadA的IgG显著增加。患病后针对LOS的IgG水平仍保持升高,而抗NadA的IgG水平在恢复期后期恢复到急性期水平。在成年人中,急性期患者血清中的抗LOS IgG水平与对照血清相似,而急性期血清中的抗NadA IgG水平显著高于对照组。针对LOS和NadA的IgG抗体水平与针对A群脑膜炎球菌菌株血清杀菌活性呈中度但显著的相关性。未来关于A群脑膜炎球菌病免疫反应的研究应考虑到人群中常见的高水平抗A群脑膜炎球菌多糖IgG,并试图阐明针对包膜下抗原的抗体在预防A群脑膜炎球菌病中的作用。