We developed a severe acute respiratory syndrome (SARS) subunit recombinant protein vaccine candidate based on a high-yielding, yeast- engineered, receptor-binding domain (RBD219-N1) of the SARS beta-coronavirus (SARS-CoV) spike (S) protein. When formulated with Alhydrogel, RBD219-N1 induced high-level neutralizing antibodies against both pseudotyped virus and a clinical (mouse-adapted) isolate of SARS-CoV. Here, we report that mice immunized with RBD219-N1/Alhydrogel were fully protected from lethal SARS-CoV challenge (0% mortality), compared to ~ 30% mortality in mice when immunized with the SARS S protein formulated with Alhydrogel, and 100% mortality in negative controls. An RBD219-N1 formulation Alhydrogel was also superior to the S protein, unadjuvanted RBD, and AddaVax (MF59-like adjuvant)-formulated RBD in inducing specific antibodies and preventing cellular infiltrates in the lungs upon SARS-CoV challenge. Specifically, a formulation with a 1:25 ratio of RBD219-N1 to Alhydrogel provided high neutralizing antibody titers, 100% protection with non-detectable viral loads with minimal or no eosinophilic pulmonary infiltrates. As a result, this vaccine formulation is under consideration for further development against SARS-CoV and potentially other emerging and re-emerging beta-CoVs such as SARS-CoV-2.

中文翻译：

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用明矾配制的酵母表达的 SARS-CoV 重组受体结合域 (RBD219-N1) 可诱导保护性免疫并降低免疫增强。

我们基于 SARS β 冠状病毒 (SARS-CoV) 刺突 (S) 的高产酵母工程受体结合域 (RBD219-N1) 开发了一种严重急性呼吸综合征 (SARS) 亚基重组蛋白候选疫苗蛋白质。当与 Alhydrogel 一起配制时，RBD219-N1 可诱导针对假型病毒和临床（小鼠适应）SARS-CoV 分离物的高水平中和抗体。在这里，我们报告说，用 RBD219-N1/Alhydrogel 免疫的小鼠完全免受致命的 SARS-CoV 攻击（0% 死亡率），而用 Alhydrogel 配制的 SARS S 蛋白免疫小鼠的死亡率约为 30%，而 100%阴性对照的死亡率。RBD219-N1 配方 Alhydrogel 也优于 S 蛋白、无佐剂 RBD、和 AddaVax（MF59 样佐剂）配制的 RBD，可在 SARS-CoV 攻击时诱导特异性抗体并防止肺部细胞浸润。具体而言，RBD219-N1 与 Alhydrogel 比例为 1:25 的制剂提供了高中和抗体滴度，100% 的保护，具有不可检测的病毒载量，且嗜酸性肺浸润最少或没有。因此，该疫苗制剂正在考虑进一步开发以对抗 SARS-CoV 和潜在的其他新兴和重新出现的 β-CoV，例如 SARS-CoV-2。