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SARS-CoV-2 protein subunit vaccination elicits potent neutralizing antibody responses
bioRxiv - Immunology Pub Date : 2020-07-31 , DOI: 10.1101/2020.07.31.228486
Marco Mandolesi , Daniel J Sheward , Leo Hanke , Junjie Ma , Pradeepa Pushparaj , Laura Perez Vidakovics , Changil Kim , Karin Loré , Xaquin Castro Dopico , Jonathan M Coquet , Gerald McInerney , Gunilla B Karlsson Hedestam , Ben Murrell

The outbreak and spread of SARS-CoV-2 (Severe Acute Respiratory Syndrome coronavirus 2), the cause of coronavirus disease 2019 (COVID-19), is a current global health emergency and a prophylactic vaccine is needed urgently. The spike glycoprotein of SARS-CoV-2 mediates entry into host cells, and thus is a target for neutralizing antibodies and vaccine design. Here we show that adjuvanted protein immunization with SARS-CoV-2 spike trimers, stabilized in prefusion conformation, results in potent antibody responses in mice and rhesus macaques with neutralizing antibody titers orders of magnitude greater than those typically measured in serum from SARS-CoV-2 seropositive humans. Neutralizing antibody responses were observed after a single dose, with exceptionally high titers achieved after boosting. Furthermore, neutralizing antibody titers elicited by a dose-sparing regimen in mice were similar to those obtained from a high dose regimen. Taken together, these data strongly support the development of adjuvanted SARS-CoV-2 prefusion-stabilized spike protein subunit vaccines.

中文翻译:

SARS-CoV-2蛋白亚基疫苗接种引起有效的中和抗体反应

SARS-CoV-2(严重急性呼吸系统综合症冠状病毒2)的爆发和传播是2019年冠状病毒疾病的病因(COVID-19),是当前全球卫生紧急情况,迫切需要预防性疫苗。SARS-CoV-2的突触糖蛋白介导进入宿主细胞,因此是中和抗体和疫苗设计的目标。在这里,我们显示,以SARS-CoV-2穗三聚体进行佐剂蛋白免疫(在融合前构象中稳定)可在小鼠和恒河猴中产生有效的抗体反应,其中和抗体滴度比在SARS-CoV- 2名血清反应阳性的人。单次给药后观察到中和抗体反应,加强后可获得极高的滴度。此外,在小鼠中通过分剂量方案引起的中和抗体滴度与从高剂量方案获得的中和抗体滴度相似。综上所述,这些数据强烈支持佐剂型SARS-CoV-2融合前稳定的刺突蛋白亚基疫苗的开发。
更新日期:2020-08-01
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