Key Points SPMs as adjuvants augment the efficacy of vaccination with NTHI P6 Ag in mice. SPM-adjuvanted vaccination efficacy rescues SHS-suppressed antibacterial immunity. Mice receiving SPM-adjuvanted vaccination rapidly clear acute infection with less lung damage. Tobacco smoke exposure is associated with multiple diseases including, respiratory diseases like asthma and chronic obstructive pulmonary disease. Tobacco smoke is a potent inflammatory trigger and is immunosuppressive, contributing to increased susceptibility to pulmonary infections in smokers, ex-smokers, and vulnerable populations exposed to secondhand smoke. Tobacco smoke exposure also reduces vaccine efficacy. Therefore, mitigating the immunosuppressive effects of chronic smoke exposure and improving the efficacy of vaccinations in individuals exposed to tobacco smoke, is a critical unmet clinical problem. We hypothesized that specialized proresolving mediators (SPMs), a class of immune regulators promoting resolution of inflammation, without being immunosuppressive, and enhancing B cell Ab responses, could reverse the immunosuppressive effects resulting from tobacco smoke exposure. We exposed mice to secondhand smoke for 8 wk, followed by a period of smoke exposure cessation, and the mice were immunized with the P6 lipoprotein from nontypeable Haemophilus influenzae, using 17-HDHA and aspirin-triggered–resolvin D1 (AT-RvD1) as adjuvants. 17-HDHA and AT-RvD1 used as adjuvants resulted in elevated serum and bronchoalveolar lavage levels of anti-P6–specific IgG and IgA that were protective, with immunized mice exhibiting more rapid bacterial clearance upon challenge, reduced pulmonary immune cell infiltrates, reduced production of proinflammatory cytokines, and less lung-epithelial cell damage. Furthermore, the treatment of mice with AT-RvD1 during a period of smoke-cessation further enhanced the efficacy of SPM-adjuvanted P6 vaccination. Overall, SPMs show promise as novel vaccine adjuvants with the ability to overcome the tobacco smoke-induced immunosuppressive effects.

中文翻译：

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专业的 Proresolving 调解员克服暴露于二手烟引起的免疫抑制

关键点 SPM 作为佐剂增强了小鼠 NTHI P6 Ag 疫苗接种的功效。SPM 佐剂的疫苗接种功效可挽救 SHS 抑制的抗菌免疫。接受 SPM 佐剂疫苗接种的小鼠迅速清除急性感染，肺损伤较少。烟草烟雾暴露与多种疾病有关，包括呼吸系统疾病，如哮喘和慢性阻塞性肺病。烟草烟雾是一种有效的炎症诱因，具有免疫抑制作用，导致吸烟者、戒烟者和暴露于二手烟的弱势人群对肺部感染的易感性增加。接触烟草烟雾也会降低疫苗效力。因此，减轻慢性烟雾暴露的免疫抑制作用并提高暴露于烟草烟雾的个体的疫苗接种效果，是一个严重的未解决的临床问题。我们假设专门的促消解介质 (SPM) 是一类促进炎症消退但不具有免疫抑制作用并增强 B 细胞抗体反应的免疫调节剂，可以逆转烟草烟雾暴露引起的免疫抑制作用。我们将小鼠暴露于二手烟 8 周，然后停止吸烟一段时间，并使用来自不可分型流感嗜血杆菌的 P6 脂蛋白对小鼠进行免疫接种，使用 17-HDHA 和阿司匹林触发的解析蛋白 D1（AT-RvD1）作为佐剂。17-HDHA 和 AT-RvD1 用作佐剂导致血清和支气管肺泡灌洗液中抗 P6 特异性 IgG 和 IgA 水平升高，具有保护作用，免疫小鼠在攻击时表现出更快的细菌清除，减少肺免疫细胞浸润，减少促炎细胞因子的产生，减少肺上皮细胞损伤。此外，在戒烟期间用 AT-RvD1 治疗小鼠进一步增强了 SPM 佐剂 P6 疫苗接种的功效。总体而言，SPM 作为新型疫苗佐剂显示出前景，能够克服烟草烟雾诱导的免疫抑制作用。