Acevedo Reinaldo, Zayas Caridad, Norheim Gunnstein, Fernández Sonsire, Cedré Barbara, Aranguren Yisabel, Cuello Maribel, Rodriguez Yaimara, González Humberto, Mandiarote Aleida, Pérez Marylin, Hernández Maritza, Hernández-Cedeño Mabel, González Domingo, Brorson Sverre-Henning, Rosenqvist Einar, Naess Lisbeth, Tunheim Gro, Cardoso Daniel, García Luis
Finlay Institute, P.O. Box 16000, La Lisa, Havana, Cuba.
Finlay Institute, P.O. Box 16000, La Lisa, Havana, Cuba.
Pharmacol Res. 2017 Jul;121:194-201. doi: 10.1016/j.phrs.2017.04.030. Epub 2017 May 8.
Meningococcal disease is caused mainly by serogroups A, B, C, Y, W of N. meningitidis. However, numerous cases of meningitis caused by serogroup X N. meningitidis (MenX) have recently been reported in several African countries. Currently, there are no licensed vaccines against this pathogen and most of the MenX cases have been caused by meningococci from clonal complex (c.c) 181. Detergent extracted meningococcal outer membrane vesicle (dOMV) vaccines have previously shown to be safe and effective against epidemics of serogroup B meningococcal disease in all age groups. The aim of this work is therefore to obtain, characterize and evaluate the vaccine potential of dOMVs derived from a MenX strain (OMVx). Three experimental lots of OMVx were prepared by deoxycholate extraction from the MenX strain BF 2/97. Size and morphology of the vesicles was determined by Dynamic Light Scattering and electron microscopy, whereas the antigenic composition was characterized by gel electrophoresis and immunoblotting. OMVx were thereafter adsorbed to aluminium hydroxide (OMVx/AL) and two doses of OMVx were administered s.c. to groups of Balb/c mice three weeks apart. The immunogenicity and functional antibody activities in sera were evaluated by ELISA (anti-OMVx specific IgG responses) and serum bactericidal activity (SBA) assay. The size range of OMVx was shown to be between 90 and 120nm, whereas some of the antigens detected were the outer membrane proteins PorA, OpcA and RmpM. The OMVx/AL elicited high anti-OMVx antibody responses with bactericidal activity and no bactericidal activity was observed in the control group of no immunised mice. The results demonstrate that OMVx are immunogenic and could form part of a future vaccine to prevent the majority of meningococcal disease in the African meningitis belt.
脑膜炎球菌病主要由脑膜炎奈瑟菌的A、B、C、Y、W血清群引起。然而,最近在几个非洲国家报告了多例由X血清群脑膜炎奈瑟菌(MenX)引起的脑膜炎病例。目前,尚无针对这种病原体的许可疫苗,且大多数MenX病例是由克隆复合体(c.c)181的脑膜炎球菌引起的。去污剂提取的脑膜炎球菌外膜囊泡(dOMV)疫苗此前已证明对所有年龄组的B血清群脑膜炎球菌病流行安全有效。因此,本研究的目的是获取、表征和评估源自MenX菌株(OMVx)的dOMV的疫苗潜力。通过用脱氧胆酸盐从MenX菌株BF 2/97中提取制备了三批实验性OMVx。通过动态光散射和电子显微镜确定囊泡的大小和形态,而通过凝胶电泳和免疫印迹表征抗原组成。此后,将OMVx吸附到氢氧化铝上(OMVx/AL),并将两剂OMVx皮下注射给Balb/c小鼠组,间隔三周。通过ELISA(抗OMVx特异性IgG反应)和血清杀菌活性(SBA)测定评估血清中的免疫原性和功能性抗体活性。结果显示OMVx的大小范围在90至120nm之间,检测到的一些抗原是外膜蛋白PorA、OpcA和RmpM。OMVx/AL引发了具有杀菌活性的高抗OMVx抗体反应,而未免疫小鼠的对照组未观察到杀菌活性。结果表明,OMVx具有免疫原性,可成为未来预防非洲脑膜炎带大多数脑膜炎球菌病疫苗的一部分。