文献检索，用中文搜 PubMed

BACKGROUND

In this pre-clinical study, we designed a candidate vaccine based on severe acute respiratory syndrome-related -coronavirus 2 (SARS-CoV-2) antigens and evaluated its safety and immunogenicity.

METHODS

SARS-CoV-2 recombinant protein antigens, including truncated spike protein (SS1, lacking the N-terminal domain of S1), receptor-binding domain (RBD), and nucleoprotein (N) were used. Immunization program was performed via injection of RBD, SS1 +RBD, and SS1 +N along with different adjuvants, Alum, AS03, and Montanide at doses of 0, 40, 80, and 120 μg at three-time points in mice, rabbits, and primates. The humoral and cellular immunity were analyzed by ELISA, VNT, splenocyte cytokine assay, and flow cytometry.

RESULTS

The candidate vaccine produced strong IgG antibody titers at doses of 80 and 120 μg on days 35 and 42. Even though AS03 and Montanide produced high-titer antibodies compared to Alum adjuvant, these sera did not neutralize the virus. Strong virus neutralization was recorded during immunization with SS1 +RBD and RBD with Alum. AS03 and Montanide showed a strong humoral and cellular immunity; however, Alum showed mild to moderate cellular responses. Ultimately, no cytotoxicity and pathologic change were observed.

CONCLUSION

These findings strongly suggest that RBD with Alum adjuvant is highly immunogenic as a potential vaccine.

背景

在这项临床前研究中，我们基于严重急性呼吸综合征相关冠状病毒 2（SARS-CoV-2）抗原设计了一种候选疫苗，并评估了其安全性和免疫原性。

方法

使用 SARS-CoV-2 重组蛋白抗原，包括截短的刺突蛋白（SS1，缺少 S1 的 N 端结构域）、受体结合域（RBD）和核蛋白（N）。通过注射 RBD、SS1+RBD 和 SS1+N 以及不同佐剂（铝佐剂、AS03 和 Montanide），在小鼠、兔和灵长类动物中进行免疫程序，剂量为 0、40、80 和 120μg，分 3 次进行。通过 ELISA、VNT、脾细胞细胞因子测定和流式细胞术分析体液和细胞免疫。

结果

候选疫苗在第 35 天和第 42 天 80 和 120μg 剂量下产生强烈的 IgG 抗体滴度。尽管 AS03 和 Montanide 产生的抗体滴度高于铝佐剂，但这些血清不能中和病毒。用 SS1+RBD 和 RBD 与铝佐剂免疫时，可记录到强烈的病毒中和作用。AS03 和 Montanide 表现出强烈的体液和细胞免疫；然而，铝佐剂表现出温和至中度的细胞反应。最终，未观察到细胞毒性和病理变化。