The spike (S) protein of coronavirus, which binds to cellular receptors and mediates membrane fusion for cell entry, is a candidate vaccine target for blocking coronavirus infection. However, some animal studies have suggested that inadequate immunization against severe acute respiratory syndrome coronavirus (SARS-CoV) induces a lung eosinophilic immunopathology upon infection. The present study evaluated two kinds of vaccine adjuvants for use with recombinant S protein: gold nanoparticles (AuNPs), which are expected to function as both an antigen carrier and an adjuvant in immunization; and Toll-like receptor (TLR) agonists, which have previously been shown to be an effective adjuvant in an ultraviolet-inactivated SARS-CoV vaccine. All the mice immunized with more than 0.5 µg S protein without adjuvant escaped from SARS after infection with mouse-adapted SARS-CoV; however, eosinophilic infiltrations were observed in the lungs of almost all the immunized mice. The AuNP-adjuvanted protein induced a strong IgG response but failed to improve vaccine efficacy or to reduce eosinophilic infiltration because of highly allergic inflammatory responses. Whereas similar virus titers were observed in the control animals and the animals immunized with S protein with or without AuNPs, Type 1 interferon and pro-inflammatory responses were moderate in the mice treated with S protein with and without AuNPs. On the other hand, the TLR agonist-adjuvanted vaccine induced highly protective antibodies without eosinophilic infiltrations, as well as Th1/17 cytokine responses. The findings of this study will support the development of vaccines against severe pneumonia-associated coronaviruses.

中文翻译：

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金纳米颗粒佐剂S蛋白诱导针对严重的急性呼吸综合征相关冠状病毒感染的强烈的抗原特异性IgG反应，但不能诱导保护性抗体并限制肺中嗜酸性粒细胞浸润。

冠状病毒的刺突蛋白（S）与细胞受体结合并介导膜融合以进入细胞，是阻断冠状病毒感染的候选疫苗靶标。但是，一些动物研究表明，针对严重急性呼吸系统综合症冠状病毒（SARS-CoV）的免疫接种不足会在感染后诱发肺嗜酸性粒细胞免疫病理。本研究评估了两种与重组S蛋白一起使用的疫苗佐剂：金纳米颗粒（AuNPs），有望在免疫中同时充当抗原载体和佐剂。和Toll样受体（TLR）激动剂，以前已显示它们是紫外线灭活的SARS-CoV疫苗中的有效佐剂。所有的小鼠都接受了大于0的免疫。在适应小鼠的SARS-CoV感染后，从SARS中逸出了5 µg不含佐剂的S蛋白；但是，几乎所有免疫小鼠的肺部都观察到嗜酸性细胞浸润。AuNP佐剂的蛋白诱导强烈的IgG应答，但是由于高度过敏的炎症应答而未能提高疫苗效力或减少嗜酸性粒细胞浸润。尽管在对照动物和用有或没有AuNPs的S蛋白免疫的动物中观察到相似的病毒滴度，但在有和没有AuNPs的S蛋白治疗的小鼠中，1型干扰素和促炎反应中等。另一方面，TLR激动剂佐剂疫苗可诱导高度保护性抗体，而没有嗜酸性粒细胞浸润以及Th1 / 17细胞因子反应。