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首页> 外文期刊>Infection and immunity >Mucosal Immunization with Recombinant Fusion Protein DnaJ-ΔA146Ply Enhances Cross-Protective Immunity against Streptococcus pneumoniae Infection in Mice via Interleukin 17A
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Mucosal Immunization with Recombinant Fusion Protein DnaJ-ΔA146Ply Enhances Cross-Protective Immunity against Streptococcus pneumoniae Infection in Mice via Interleukin 17A

机译：重组融合蛋白DnaJ-ΔA146Ply的粘膜免疫增强了通过白介素17A对小鼠肺炎链球菌感染的交叉保护性免疫。

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Pneumolysin (Ply) and its variants are protective against pneumococcal infections in animal models, and as a Toll-like receptor 4 agonist, pneumolysin has been reported to be a mucosal adjuvant. DnaJ has been approved as a useful candidate vaccine protein; we therefore designed novel fusion proteins of DnaJ with a form of Ply that has a deletion of A146 (ΔA146Ply-DnaJ [the C terminus of ΔA146Ply connected with the N terminus of DnaJ] and DnaJ-ΔA146Ply [the C terminus of DnaJ connected with the N terminus of ΔA146Ply]) to test whether they are protective against focal and lethal pneumococcal infections and their potential protective mechanisms. The purified proteins were used to intranasally immunize the animals without additional adjuvant. Immunization with DnaJ-ΔA146Ply or DnaJ plus ΔA146Ply (Ply with a single deletion of A146) could significantly reduce S. pneumoniae colonization in the nasopharynx and lung relative with DnaJ alone. Additionally, we observed the best protection for DnaJ-ΔA146Ply-immunized mice after challenge with lethal doses of S. pneumoniae strains, which was comparable to that achieved by PPV23. Mice immunized with DnaJ-ΔA146Ply produced significantly higher levels of anti-DnaJ IgG in serum and secretory IgA (sIgA) in saliva than those immunized with DnaJ alone. The production of IL-17A was also striking in DnaJ-ΔA146Ply-immunized mice. IL-17A knockout (KO) mice did not benefit from DnaJ-ΔA146Ply immunization in colonization experiments, and sIgA production was impaired in IL-17A KO mice. Collectively, our results indicate a mucosal adjuvant potential for ΔA146Ply and that, without additional adjuvant, DnaJ-ΔA146Ply fusion protein exhibits extensive immune stimulation and is effective against pneumococcal challenges, properties which are partially attributed to the IL-17A-mediated immune responses.
机译：肺炎球菌溶血素（Ply）及其变体在动物模型中对肺炎球菌感染具有保护作用，据报道，作为Toll样受体4激动剂，肺炎球菌溶血素是一种粘膜佐剂。 DnaJ已被批准为有用的候选疫苗蛋白。因此，我们设计了一种新的DnaJ融合蛋白，其融合形式为Ply，缺失了A146（ΔA146Ply-DnaJ[ΔA146Ply的C端与DnaJ的N端相连]和DnaJ-ΔA146Ply[DnaJ的C端与Ana相连的D端] N端[ΔA146Ply]），以测试它们是否对局灶性和致命性肺炎球菌感染具有保护作用，以及它们潜在的保护机制。纯化的蛋白质无需其他佐剂即可用于鼻内免疫动物。相对于单独的DnaJ，用DnaJ-ΔA146Ply或DnaJ加ΔA146Ply（仅缺失A146的Ply）免疫接种可显着减少鼻咽和肺中的肺炎链球菌定植。此外，在用致死剂量的肺炎链球菌菌株攻击后，我们观察到了对DnaJ-ΔA146Ply免疫小鼠的最佳保护，这与PPV23所获得的保护相当。与仅用DnaJ免疫的小鼠相比，用DnaJ-ΔA146Ply免疫的小鼠血清和唾液中分泌型IgA（sIgA）产生的抗DnaJ IgG水平明显更高。在DnaJ-ΔA146Ply免疫的小鼠中，IL-17A的产生也很惊人。在定植实验中，IL-17A敲除（KO）小鼠未从DnaJ-ΔA146Ply免疫中受益，并且IL-17A KO小鼠的sIgA产生受到损害。总的来说，我们的结果表明ΔA146Ply的粘膜佐剂潜力，并且在没有其他佐剂的情况下，DnaJ-ΔA146Ply融合蛋白表现出广泛的免疫刺激作用，并有效抵抗肺炎球菌攻击，其特性部分归因于IL-17A介导的免疫反应。

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