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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Serotype-independent pneumococcal experimental vaccines that induce cellular as well as humoral immunity
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Serotype-independent pneumococcal experimental vaccines that induce cellular as well as humoral immunity

机译：不依赖血清型的肺炎球菌实验疫苗，可诱导细胞和体液免疫

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For prevention of Streptococcus pneumoniae (pneumococcus) infections in infancy, protein-conjugated capsular polysaccharide vaccines provide serotype-specific, antibody-mediated immunity but do not cover all of the 90+ capsule serotypes. Therefore, microbiologists have sought protective noncapsular antigens common to all strains. Alternatively, we investigated killed cells of a noncapsulated strain, which expose many such common antigens.Given to mice intranasally, this vaccine elicits antibody-independent, CD4+ T lymphocyte-dependent accelerated clearance of pneumococci of various serotypes from the nasopharynx mediated by the cytokine IL-17A. Such immunity may reproduce the natural resistance that develops in infants before capsular antibodies arise. Given by injection, the killed cell vaccine induces bifunctional immunity: plasma antibodies protective against fatal pneumonia challenge, as well as IL-17A-mediated nasopharyngeal clearance.Human testing of this inexpensive candidate vaccine by intramuscular injection is planned. Bacterial cellular vaccines are complexa challenge for reproducibility. However, when several known protective antigens were deleted, the killed pneumococcal vaccine was still protective. This antigenic redundancy may prevent vaccine escape variants by recombinational loss, which is frequent in pneumococcus. Biochemically defined immunogens with bifunctional activity have also been devised. These immunogens are three-component conjugates in which cell wall teichoic acid (a common antigen capable of T cell activation) is coupled to a genetic fusion of two common pneumococcal proteins: a protective surface antigen and a derivative of pneumolysin, which provides TLR4 agonist activity and induces antitoxic immunity. Such constructs induce accelerated clearance when given intranasally and induce both immune mechanisms when injected. The defined composition permits analysis of structure-function activity.
机译：为了预防婴儿期的肺炎链球菌（肺炎球菌）感染，蛋白偶联的荚膜多糖疫苗可提供血清型特异性抗体介导的免疫力，但不能覆盖所有90多种胶囊型血清型。因此，微生物学家寻求了所有菌株共有的保护性非荚膜抗原。或者，我们研究了一种非封装菌株的杀死细胞，该细胞暴露了许多此类常见抗原。该疫苗经鼻内注射给小鼠，引起由细胞因子IL介导的鼻咽中多种血清型肺炎球菌的抗体依赖性，CD4 + T淋巴细胞依赖性加速清除。 -17A。此类免疫力可以重现荚膜抗体出现之前在婴儿体内产生的自然抵抗力。通过注射后，杀死的细胞疫苗可诱导双功能免疫：抗致命性肺炎攻击的血浆抗体以及IL-17A介导的鼻咽清除。计划通过肌肉注射对该廉价候选疫苗进行人体测试。细菌细胞疫苗是可重复性的复杂挑战。但是，当删除了几种已知的保护性抗原时，被杀死的肺炎球菌疫苗仍然具有保护性。这种抗原冗余可以通过重组损失防止疫苗逃逸变体，重组损失在肺炎球菌中很常见。还已经设计了具有双功能活性的生化定义的免疫原。这些免疫原是三成分的偶联物，其中细胞壁硫壁酸（一种能够激活T细胞的常见抗原）与两种常见的肺炎球菌蛋白的遗传融合结合在一起：一种保护性表面抗原和一种提供TLR4激动剂活性的肺炎球菌溶血素。并诱导抗毒免疫力。当鼻内给予时，此类构建体诱导加速清除，并在注射时诱导两种免疫机制。定义的成分可以分析结构功能活性。

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