IMMUNIZATION WITH SYNTHETIC PEPTIDES CONTAINING EPITOPES OF THE CLASS-1 OUTER-MEMBRANE PROTEIN OF NEISSERIA-MENINGITIDIS - PRODUCTION OF BACTERICIDAL ANTIBODIES ON IMMUNIZATION WITH A CYCLIC PEPTIDE
IMMUNIZATION WITH SYNTHETIC PEPTIDES CONTAINING EPITOPES OF THE CLASS-1 OUTER-MEMBRANE PROTEIN OF NEISSERIA-MENINGITIDIS - PRODUCTION OF BACTERICIDAL ANTIBODIES ON IMMUNIZATION WITH A CYCLIC PEPTIDE
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DOI：
10.1099/00221287-139-8-1729
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发表时间：
1993-08-01
期刊：
影响因子：
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通讯作者：
HECKELS, JE
中科院分区：
文献类型：
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作者：
CHRISTODOULIDES, M;MCGUINNESS, BT;HECKELS, JE
脑膜炎奈瑟氏球菌的1类外膜蛋白是亚型特异性杀菌性单克隆抗体（mAb）的靶标。由这些抗体识别的表位先前已被映射到对应于被认为暴露在蛋白质的表面暴露环的顶点处的序列的线性肽。在这项工作中，已经合成了几种含有亚型P1.16b表位的合成肽，目的是诱导类似于mAb反应性的多克隆免疫应答。最初，合成9和15个氨基酸残基的肽，并在偶联至载体蛋白后用于免疫。所得抗血清与合成线性十肽的反应性类似于先前用保护性mAb进行的表位作图实验中所见。然而，尽管诱导了具有所需特异性的抗体，但抗血清与外膜中的天然蛋白质的反应很差，并且是非杀菌性的。然后合成由1类蛋白的整个表面暴露的环4组成的36聚体肽，并作为（i）游离肽、（ii）与载体偶联的肽和（iii）经历环化的肽用于免疫，试图将其限制为可能更接近于天然环结构的构象。与针对线性肽产生的抗血清相反，通过用36聚体环肽免疫产生的抗体不与mAb识别的线性肽反应，而是似乎识别构象决定簇。该抗血清促进了补体介导的对同源脑膜炎球菌菌株的杀菌作用，证明了合成肽免疫原诱导针对B群脑膜炎球菌的保护性免疫应答的潜力。
The class 1 outer-membrane protein of Neisseria menigitidis is the target for subtype-specific, bactericidal monoclonal antibodies (mAbs). The epitopes recognized by these antibodies have been mapped previously to linear peptides corresponding to the sequences thought to be exposed at the apices of surface-exposed loops of the protein. In this work several synthetic peptides containing the subtype P1.16b epitope have been synthetized with the aim of inducing a polyclonal immune response resembling the reactivity of the mAbs. Initially, peptides of 9 and 15 amino acid residues were synthesized and used for immunization after coupling to a carrier protein. The reactivity of the resulting antisera, with synthetic linear decapeptides, resembled that seen in previous epitope mapping experiments with the protective mAbs. However, despite the induction of antibodies having the desired specificity, the antisera reacted poorly with the native protein in outer membranes, and were non-bactericidal. A 36mer peptide, consisting of the entire surface-exposed loop 4 of the class 1 protein was then synthesized and used for immunization as (i) free peptide, (ii) peptide coupled to carrier and (iii) peptide subjected to cyclization, in an attempt to restrict it to conformations that might more closely resemble the native loop structure. In contrast to antisera raised against linear peptides, antibodies raised by immunization with the 36mer cyclic peptide, did not react with linear peptides recognized by the mAbs, but instead appeared to recognize conformational determinants. This antiserum promoted complement-mediated bactericidal killing of the homologous meningococcal strain, demonstrating the potential of synthetic peptide immunogens for inducing a protective immune response against group B meningococci.