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首页> 美国卫生研究院文献>Infection and Immunity >Specificity of human bactericidal antibodies against PorA P1.716 induced with a hexavalent meningococcal outer membrane vesicle vaccine.
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Specificity of human bactericidal antibodies against PorA P1.716 induced with a hexavalent meningococcal outer membrane vesicle vaccine.

机译：用六价脑膜炎球菌外膜囊泡疫苗诱导的针对PorA P1.716的人杀菌抗体的特异性。

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摘要

A set of isogenic strains was constructed from the meningococcal reference strain H44/76 (B:15:P1.7,16) which differed only in their outer membrane protein (OMP) compositions. First, three isogenic strains lacking the expression of either class 3 (PorB) or class 4 (RmpM) OMP or both were obtained. Second, three isogenic class 1 OMP loop-deficient strains of H44/76 lacking the predicted loop 1 or 4 or both of class 1 OMP (PorA) were obtained. Third, three isogenic class 1 OMP strains which differed by point mutations in the predicted loop 4 of subtype P1.16 were constructed. Strains were constructed through transformation with gene constructs made in Escherichia coli and their homologous recombination into the meningococcal chromosome. This study describes the contribution of one of the six class 1 OMPs, PorA P1.7,16, in the development of bactericidal antibodies after a single immunization of adult volunteers with 50 or 100 micrograms of protein within a hexavalent PorA outer membrane vesicle vaccine. PorA-, PorB-, and RpmM-deficient isogenic strains were used to define the human immune response against PorA. The loop-deficient isogenic strains were used to define the contribution of loops 1 and 4 of PorA in the development of bactericidal anti-PorA antibodies. The isogenic strains carrying a point mutation in loop 4 were used to study the cross-reactivity of the induced bactericidal antibodies against target strains showing microheterogeneity. The results indicate that a single immunization with the hexavalent PorA vaccine induced a dose-dependent bactericidal immune response, which is directed mainly against PorA. The epitope specificity of antibodies is directed mostly against loop 1, although loop 4 and as-yet-unidentified epitopes of PorA P1.7,16 are also involved.
机译：从脑膜炎球菌参考菌株H44 / 76（B：15：P1.7,16）构建了一组同基因菌株，它们仅在外膜蛋白（OMP）组成上有所不同。首先，获得了三个缺乏3类（PorB）或4类（RmpM）OMP或两者表达的同基因菌株。其次，获得了三个等基因的H44 / 76 1类OMP环缺陷型菌株，它们缺少1类OMP的预测环1或4或两者，都缺乏（PorA）。第三，构建了三个等基因的1类OMP菌株，它们在P1.16亚型的预测环4中的点突变不同。通过用在大肠杆菌中制备的基因构建体转化并将它们同源重组到脑膜炎球菌染色体中来构建菌株。这项研究描述了六种1类OMP之一PorA P1.7,16在六价PorA外膜囊泡疫苗中用50或100微克蛋白质对成年志愿者进行单次免疫后对杀菌抗体的发展的贡献。缺乏PorA，PorB和RpmM的同基因菌株用于定义人类针对PorA的免疫反应。缺乏环的等基因菌株用于确定PorA的环1和4在杀菌抗PorA抗体研发中的作用。使用在环4中携带点突变的同基因菌株来研究诱导的杀菌抗体与显示微异质性的目标菌株的交叉反应性。结果表明，用六价PorA疫苗单次免疫诱导了剂量依赖性杀菌免疫反应，该反应主要针对PorA。抗体的表位特异性主要针对环1，尽管环4和PorA P1.7,16尚未鉴定的表位也涉及。

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