Department of Biomedical Sciences, College of Veterinary Medicine, Iowa State University, Ames, IA, United States.
Department of Veterinary Microbiology and Preventive Medicine, College of Veterinary Medicine, Iowa State University, Ames, IA, United States.
Front Immunol. 2021 Mar 11;12:637982. doi: 10.3389/fimmu.2021.637982. eCollection 2021.
A novel betacoronavirus (SARS-CoV-2) that causes severe pneumonia emerged through zoonosis in late 2019. The disease, referred to as COVID-19, has an alarming mortality rate and it is having a devastating effect on the global economy and public health systems. A safe, effective vaccine is urgently needed to halt this pandemic. In this study, immunogenicity of the receptor binding domain (RBD) of spike (S) glycoprotein was examined in mice. Animals were immunized with recombinant RBD antigen intraperitoneally using three different adjuvants (Zn-chitosan, Alhydrogel, and Adju-Phos), and antibody responses were followed for over 5 months. Results showed that potent neutralizing antibodies (nAbs) can be induced with 70% neutralization titer (NT) of ~14,580 against live, infectious viruses. Although antigen-binding antibody titers decreased gradually over time, sufficiently protective levels of nAbs persisted (NT >2,430) over the 5-month observation period. Results also showed that adjuvants have profound effects on kinetics of nAb induction, total antibody titers, antibody avidity, antibody longevity, and B-cell epitopes targeted by the immune system. In conclusion, a recombinant subunit protein immunogen based on the RBD is a highly promising vaccine candidate. Continued evaluation of RBD immunogenicity using different adjuvants and vaccine regimens could further improve vaccine efficacy.
一种新型贝塔冠状病毒（SARS-CoV-2）通过动物传染病于 2019 年末引发严重肺炎。这种疾病被称为 COVID-19，其死亡率令人震惊，对全球经济和公共卫生系统造成了毁灭性影响。急需一种安全、有效的疫苗来阻止这种大流行。在这项研究中，研究了刺突（S）糖蛋白受体结合域（RBD）的免疫原性。使用三种不同佐剂（Zn-壳聚糖、Alhydrogel 和 Adju-Phos）通过腹腔内免疫将重组 RBD 抗原接种到动物体内，并对抗体反应进行了超过 5 个月的跟踪。结果表明，用 70%中和效价（NT）约 14580 可以诱导出有效的中和抗体（nAbs），针对活的、感染性病毒。尽管随着时间的推移抗原结合抗体滴度逐渐下降，但在 5 个月的观察期内，仍保持足够的保护性 nAb 水平（NT>2430）。结果还表明，佐剂对 nAb 诱导的动力学、总抗体滴度、抗体亲和力、抗体寿命和免疫系统靶向的 B 细胞表位有深远影响。总之，基于 RBD 的重组亚单位蛋白免疫原是一种很有前途的疫苗候选物。使用不同佐剂和疫苗方案继续评估 RBD 的免疫原性可以进一步提高疫苗的效力。
