树突状细胞靶向TLR3的预防性疫苗改善小鼠SARS-CoV感染模型中的嗜酸性肺炎

Q3 Medicine ImmunoHorizons Pub Date : 2022-04-01 DOI:10.4049/immunohorizons.2200020
N. Iwata-Yoshikawa, N. Nagata, Hiromi Takaki, M. Matsumoto, Tadaki Suzuki, H. Hasegawa, T. Seya
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引用次数: 3

摘要

在小鼠BALB/c模型中检测了假定的冠状病毒刺突蛋白和ARNAX (tlr3特异性树突状细胞佐剂)亚组分疫苗,并与刺突蛋白+明胶进行了比较。生存率、体重、血液中病毒中和抗体滴度和肺中病毒滴度作为预后指标进行评估。感染后10 d组织病理学观察肺嗜酸性粒细胞浸润程度。结果表明:(1)佐剂是疫苗感染后完全恢复所必需的;(2)与明矾相比,ARNAX具有最佳的体重恢复效果;(3)ARNAX对嗜酸性肺炎的改善效果最佳;(4)嗜酸性粒细胞浸润评分与血液中和抗体滴度或肺病毒滴度无关。尽管TLR3疫苗与肺嗜酸性粒细胞浸润之间的病理联系尚不清楚,但严重急性呼吸综合征介导的嗜酸性粒细胞性肺炎可以通过ARNAX预先诱导树突状细胞启动而被阻断。
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Prophylactic Vaccine Targeting TLR3 on Dendritic Cells Ameliorates Eosinophilic Pneumonia in a Mouse SARS-CoV Infection Model
Putative subcomponent vaccines of severe acute respiratory syndrome coronavirus spike protein and ARNAX (TLR3-specific adjuvant for priming dendritic cells) were examined and compared with spike protein + Alum in a mouse BALB/c model. Survival, body weight, virus-neutralizing Ab titer in the blood, and viral titer in the lung were evaluated for prognosis markers. The infiltration degrees of eosinophils in the lung were histopathologically monitored at 10 d postinfection. The results were: (1) adjuvant was essential in vaccines to achieve a complete recovery from infection, (2) ARNAX displayed optimal body weight recovery compared with Alum, (3) ARNAX was optimal for the amelioration of eosinophilic pneumonia, and (4) the eosinophil infiltration score was not associated with the neutralizing Ab titer in the blood or viral titer in the lung. Although the pathological link between the TLR3 vaccine and lung eosinophil infiltration remains unclear, severe acute respiratory syndrome–mediated eosinophilic pneumonia can be blocked by the prior induction of dendritic cell priming by ARNAX.
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CiteScore
3.70
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4 weeks
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