Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden.
Division of Medical Virology, Institute of Infectious Diseases and Molecular Medicine, University of Cape Town, Cape Town, South Africa.
Cell Rep Med. 2021 Apr 20;2(4):100252. doi: 10.1016/j.xcrm.2021.100252. Epub 2021 Apr 5.
The outbreak and spread of SARS-CoV-2 (severe acute respiratory syndrome-coronavirus-2) is a current global health emergency, and effective prophylactic vaccines are needed urgently. The spike glycoprotein of SARS-CoV-2 mediates entry into host cells, and thus is the target of neutralizing antibodies. Here, we show that adjuvanted protein immunization with soluble SARS-CoV-2 spike trimers, stabilized in prefusion conformation, results in potent antibody responses in mice and rhesus macaques, with neutralizing antibody titers exceeding those typically measured in SARS-CoV-2 seropositive humans by more than one order of magnitude. Neutralizing antibody responses were observed after a single dose, with exceptionally high titers achieved after boosting. A follow-up to monitor the waning of the neutralizing antibody responses in rhesus macaques demonstrated durable responses that were maintained at high and stable levels at least 4 months after boosting. These data support the development of adjuvanted SARS-CoV-2 prefusion-stabilized spike protein subunit vaccines.
严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）的爆发和传播是当前的全球卫生紧急事件，急需有效的预防性疫苗。SARS-CoV-2 的刺突糖蛋白介导病毒进入宿主细胞，因此是中和抗体的靶标。在这里，我们表明，与预融合构象稳定的可溶性 SARS-CoV-2 刺突三聚体佐剂的蛋白免疫接种会在小鼠和恒河猴中引发强烈的抗体反应，中和抗体滴度超过通常在 SARS-CoV-2 血清阳性的人类中测量的滴度超过一个数量级。单次剂量后即可观察到中和抗体反应，加强免疫后可获得异常高的滴度。后续监测恒河猴中和抗体反应的衰减情况表明，加强免疫后至少 4 个月，中和抗体反应仍保持在高且稳定的水平。这些数据支持开发佐剂增强的 SARS-CoV-2 预融合稳定的刺突蛋白亚单位疫苗。
