Bactericidal activity of antibodies elicited against the Neisseria meningitidis 37-kDa ferric binding protein (FbpA) with different adjuvants
Bactericidal activity of antibodies elicited against the Neisseria meningitidis 37-kDa ferric binding protein (FbpA) with different adjuvants
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DOI：
10.1016/s0928-8244(97)00109-0
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发表时间：
1998-01-01
影响因子：
--
通讯作者：
Ferreirós, CM
中科院分区：
文献类型：
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作者：
Gómez, JA;Criado, MT;Ferreirós, CM
用铁亲和色谱法将来自三种脑膜炎奈瑟氏球菌菌株的37-kDa铁结合蛋白FbpA纯化至均一，并使用四种不同的佐剂：氢氧化铝、弗氏佐剂、皂苷Quil-A和Ribi佐剂系统（RAS）对小鼠进行免疫。还包括在没有佐剂的情况下免疫的对照。获得的所有血清对脑膜炎球菌FbpA都是单特异性的，当使用RAS和Quil-A时抗体滴度更高（256），PBS导致滴度类似于弗氏（Freund's）的滴度（64），并且令人惊讶的是，当使用氢氧化铝（唯一批准用于人类的佐剂）时没有引发抗体。所有的抗FbpA血清结合完整的脑膜炎球菌细胞，表现出完全的交叉反应性，但抗FbpA抗体的杀菌活性，首次在这项工作中证明，是低的（32%的同源菌株的杀伤），和免疫球蛋白同种型的分析表明，非杀菌IgG 1占主导地位。结果证实，FbpA是表面暴露的、抗原性的，并且能够引发杀菌抗体，尽管在测试的条件下和使用测试的佐剂时，杀伤效力低并且交叉杀伤非常可变，不支持在疫苗制剂中包含该蛋白质。然而，鉴于FbpA在奈瑟氏球菌属中的高度保守性、其表面暴露及其抗原性，用对应于暴露的表位的肽和/或新佐剂系统进行免疫的研究可以改善对该蛋白质的杀菌应答，使其适合于疫苗开发。(C)1998年，欧洲微生物学会联合会。出版社：Elsevier Science B. V.
The 37-kDa ferric binding protein, FbpA, from three Neisseria meningitidis strains was purified to homogeneity with iron-affinity chromatography and used for immunisation of mice employing four different adjuvants: aluminium hydroxide, Freund's, the saponin Quil-A, and a Ribi adjuvant system (RAS). Controls immunised without adjuvant were also included. All sera obtained were monospecific for the meningococcal FbpA, with antibody titres higher when RAS and Quil-A were used (256), PBS resulting in titres similar to those of Freund's (64), and, surprisingly, with no antibodies elicited when aluminium hydroxide, the only approved adjuvant for use in humans, was used. All anti-FbpA sera bound to intact meningococcal cells, showing a complete cross-reactivity, but the bactericidal activity of anti-FbpA antibodies, demonstrated for the first time in this work, was low (32% of killing with the homologous strain), and the analysis of immunoglobulin isotypes showed that the non-bactericidal IgG1 was predominant. The results confirm that the FbpA is surface-exposed, antigenic, and able to elicit bactericidal antibodies, although, in the conditions and with the adjuvants tested, killing efficacy was low and cross-killing was very variable, not supporting the inclusion of this protein in vaccine formulations. Nevertheless, given the high conservation of the FbpA in the genus Neisseria ia, its surface exposure and its antigenicity, studies on immunisation with peptides corresponding to the exposed epitopes and/or new adjuvant systems could improve the bactericidal response to this protein, making it suitable for vaccine development. (C) 1998 Federation of European Microbiological Societies. Published by Elsevier Science B.V.