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首页> 外文期刊>Infection and immunity >Synthesis and Characterization of Lipooligosaccharide-Based Conjugate Vaccines for Serotype B Moraxella catarrhalis
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Synthesis and Characterization of Lipooligosaccharide-Based Conjugate Vaccines for Serotype B Moraxella catarrhalis

机译:乙脂性粘膜炎莫拉菌的基于脂寡糖的结合疫苗的合成与表征

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Moraxella catarrhalis is an important cause of otitis media in children and respiratory tract infections in the elderly. Lipooligosaccharide (LOS) is a major surface antigen of the bacterium that elicits bactericidal antibodies. Serological studies show that three major LOS types (A, B, and C) have been identified among clinical isolates. Our previous studies demonstrated that the type A LOS-based conjugates were immunogenic in animals. In this study, LOS from type B strain 26397 was detoxified and conjugated to tetanus toxoid (TT) or a cross-reactive mutant (CRM) of diphtheria toxin to form detoxified LOS (dLOS)-TT and dLOS-CRM, respectively, as vaccine candidates. The molar ratios of dLOS to TT and CRM in the conjugates were 43:1 and 19:1, respectively, while both weight ratios were around 0.9. The antigenicity of the conjugates was similar to that of the LOS, as determined by enzyme-linked immunosorbent assay using a rabbit antiserum to strain 26397. Subcutaneous immunization with each conjugate elicited a 180- to 230-fold rise of serum anti-LOS immunoglobulin G in mice and >2,000-fold rise in rabbits. In addition, both mouse and rabbit antisera showed elevated complement-mediated bactericidal activity against the homologous strain, and a representative rabbit antiserum showed bactericidal activity against nine of twelve clinical isolates studied. The bactericidal activity of the rabbit antiserum can be fully inhibited by the type B LOS but not the A or C LOS. These results indicate that the type B LOS-based conjugates can be used as vaccine components for further investigation.
机译:卡他莫拉菌是儿童中耳炎和老年人呼吸道感染的重要原因。脂寡糖(LOS)是引起杀菌抗体的细菌的主要表面抗原。血清学研究表明,在临床分离株中已鉴定出三种主要的LOS类型(A,B和C)。我们以前的研究表明,基于A型LOS的结合物在动物中具有免疫原性。在这项研究中,将来自B型菌株26397的LOS解毒并与破伤风类毒素(TT)或白喉毒素的交叉反应突变体(CRM)结合,分别形成解毒的LOS(dLOS)-TT和dLOS-CRM,作为疫苗考生。缀合物中dLOS与TT和CRM的摩尔比分别为43:1和19:1,而两种重量比均约为0.9。结合物的抗原性类似于LOS的抗原性,这是通过使用酶联免疫吸附试验使用兔抗血清对26397菌株测定的。用每种结合物进行皮下免疫会引起血清抗LOS免疫球蛋白G升高180到230倍。在老鼠身上,兔子上升> 2,000倍。此外,小鼠和兔抗血清均显示出升高的补体介导的针对同源菌株的杀菌活性,并且代表性的兔抗血清显示出对所研究的十二种临床分离株中的九种的杀菌活性。 B型LOS可以完全抑制兔抗血清的杀菌活性,但A或C LOS则不能。这些结果表明,基于B LOS的B型结合物可以用作疫苗成分进行进一步研究。

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