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首页> 外文期刊>Vaccine >Post-exposure immunization against Francisella tularensis membrane proteins augments protective efficacy of gentamicin in a mouse model of pneumonic tularemia.
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Post-exposure immunization against Francisella tularensis membrane proteins augments protective efficacy of gentamicin in a mouse model of pneumonic tularemia.

机译：暴露后对土拉弗朗西斯菌膜蛋白的免疫增强了庆大霉素在肺炎性图拉血病小鼠模型中的保护作用。

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Successful treatment of pneumonic infection with Francisella tularensis, the causative agent of tularemia, requires rapid initiation of antibiotic therapy, yet even then treatment failures may occur. Consequently, new treatments are needed to enhance the effectiveness of antimicrobial therapy for acute pneumonic tularemia. In a prior study, immunization with F. tularensis membrane protein fraction (MPF) antigens 3 days prior to challenge was reported to induce significant protection from inhalational challenge. We therefore hypothesized that MPF immunization might also be effective in enhancing infection control if combined with antibiotic therapy and administered after infection as post-exposure immunotherapy. To address this question, a 24 h post-exposure treatment model of acute pulmonary Schu S4 strain of F. tularensis infection in BALB/c mice was used. Following exposure, mice were immunized with MPF and treated with low-dose gentamicin, alone or in combination and the effects on survival, bacterial burden and dissemination were assessed. We found that immunization with MPF significantly increased the effectiveness of subtherapeutic gentamicin for post-exposure treatment of pneumonic tularemia, with 100% of combination-treated mice surviving long-term. Bacterial burdens in the liver and spleen were significantly reduced in combination MPF-gentamicin treated mice at 7 days after challenge. Passively transferred antibodies against MPF antigens also increased the effectiveness of gentamicin therapy. Thus, we concluded that post-exposure immunization with MPF antigens was an effective means of enhancing conventional antimicrobial therapy for pneumonic tularemia.
机译：tularemia的病原体 Tularcisella tularensis 要成功治疗肺炎感染，需要迅速开始抗生素治疗，但即使这样，治疗仍可能失败。因此，需要新的治疗方法来增强抗菌治疗急性肺炎性尿毒症的有效性。在先前的研究中，用iF免疫。据报道，攻击前3天，土拉菌膜蛋白成分（MPF）抗原可诱导对吸入性攻击的显着保护。因此，我们假设，如果将MPF免疫与抗生素治疗相结合并在感染后作为暴露后免疫疗法进行管理，那么MPF免疫也可能有效地增强了感染控制。为了解决这个问题，建立了急性肺Schu S4 F株的24小时暴露后治疗模型。使用BALB / c小鼠中的土拉菌感染。暴露后，用MPF免疫小鼠并单独或组合用低剂量庆大霉素治疗，并评估其对存活，细菌负担和传播的影响。我们发现，用MPF进行的免疫显着提高了庆大霉素亚治疗暴露于肺炎性Tularemia的暴露后治疗的效率，其中100％的联合治疗小鼠能够长期存活。攻击后第7天，经MPF-庆大霉素联合治疗的小鼠的肝脏和脾脏细菌负担明显减少。被动转移的针对MPF抗原的抗体也提高了庆大霉素治疗的有效性。因此，我们得出结论，用MPF抗原进行暴露后免疫是增强针对肺炎性Tularemia的常规抗菌治疗的有效手段。

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