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首页> 外文期刊>Infection and immunity >Protection against Pneumococcal Colonization and Fatal Pneumonia by a Trivalent Conjugate of a Fusion Protein with the Cell Wall Polysaccharide
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Protection against Pneumococcal Colonization and Fatal Pneumonia by a Trivalent Conjugate of a Fusion Protein with the Cell Wall Polysaccharide

机译：三价结合融合蛋白与细胞壁多糖对肺炎球菌定植和致命性肺炎的保护作用

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Cell wall polysaccharide (CWPS), pneumolysin, and surface adhesin A (PsaA) are antigens common to virtually all serotypes of Streptococcus pneumoniae (pneumococcus), and all have been studied separately for use in protection. Previously we showed that protection against nasopharyngeal (NP) colonization by intranasal vaccination of mice with killed pneumococci is mediated by TH17 cells and correlates with interleukin-17A (IL-17A) expression by T cells in vitro; we have also shown that CWPS and other species-common antigens protect against colonization by a similar mechanism. Here we made a fusion protein of PsaA with the pneumolysin nontoxic derivative PdT and then coupled CWPS to the fusion protein, aiming to enhance immune responses to all three antigens. When given intranasally with cholera toxin adjuvant, the fusion conjugate induced higher serum antibody titers and greater priming for IL-17A responses than an equimolar mixture of the three antigens. The conjugate administered intranasally protected mice against experimental NP colonization by a strain of serotype 6B, while mice immunized with the mixture or with bivalent conjugates were not protected. Subcutaneous immunization with the conjugate and alum adjuvant likewise induced higher antibody titers than the mixture, primed for IL-17A responses, and reduced colonization. The conjugate, but not the antigen mixture, fully protected mice from fatal pneumonia caused by a highly virulent serotype 3 strain. Thus, a covalent construct of three antigens common to all serotypes exhibits protection with both mucosal and systemic administration.
机译：细胞壁多糖（CWPS），肺炎球菌溶血素和表面粘附素A（PsaA）实际上是所有肺炎链球菌（emem）血清型（肺炎球菌）共有的抗原，并且已分别进行了研究以用于保护。先前我们表明，经鼻内接种灭活肺炎球菌的小鼠鼻内接种疫苗对鼻咽（NP）定植的保护作用是由T H 17细胞介导的，并且与体外T细胞表达白介素17A（IL-17A）相关;我们还表明，CWPS和其他物种共有的抗原可通过类似的机制防止定居。在这里，我们制备了PsaA与肺炎球菌溶血素无毒衍生物PdT的融合蛋白，然后将CWPS偶联到融合蛋白上，旨在增强对所有三种抗原的免疫应答。当与霍乱毒素佐剂鼻内给予时，与三种抗原的等摩尔混合物相比，融合缀合物诱导更高的血清抗体滴度和更大的IL-17A反应引发。经鼻内施用的缀合物保护小鼠免受血清型6B菌株的实验性NP定植，而用混合物或二价缀合物免疫的小鼠则不受保护。用缀合物和明矾佐剂进行的皮下免疫同样诱导了比混合物更高的抗体效价，引发了针对IL-17A的反应，并减少了定植。结合物（而不是抗原混合物）完全保护了小鼠免受致命的3型强毒血清型肺炎的侵害。因此，所有血清型共有的三种抗原的共价构建体在粘膜和全身给药中均显示出保护作用。

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