Rapid evaluation of heterologous chimeric RBD-dimer mRNA vaccine for currently-epidemic Omicron sub-variants as booster shot after inactivated vaccine

IF 3.5 Q1 PUBLIC, ENVIRONMENTAL & OCCUPATIONAL HEALTH Biosafety and Health Pub Date : 2023-04-01 DOI:10.1016/j.bsheal.2023.02.002
Qian Chen , Pei Du , Yuxuan Han , Xuehui Ma , Rong Zhang , Xiaoyu Rong , Xu Zhao , Renyi Ma , Huiting Yang , Anqi Zheng , Qingrui Huang , Jinghua Yan , Hui Wang , Xin Zhao , Lianpan Dai , George F. Gao , Qihui Wang
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引用次数: 3

Abstract

With continuous mutations of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the severe immune escape of Omicron sub-variants urges the development of next-generation broad-spectrum vaccines, especially as booster jabs after high-level vaccination coverage of inactivated vaccines in China and many other countries. Previously, we developed a coronavirus disease 2019 (COVID-19) protein subunit vaccine ZF2001® based on the tandem homo-prototype receptor-binding domain (RBD)-dimer of the SARS-CoV-2 spike protein. We upgraded the antigen into a hetero-chimeric prototype (PT)-Beta or Delta-BA.1 RBD-dimer to broaden the cross-protection efficacy and prove its efficiency with protein subunit and mRNA vaccine platforms. Herein, we further explored the hetero-chimeric RBD-dimer mRNA vaccines and evaluated their broad-spectrum activities as booster jabs following two doses of inactivated vaccine (IV) in mice. Our data demonstrated that the chimeric vaccines significantly boosted neutralizing antibody levels and specific T-cell responses against the variants, and PT-Beta was superior to Delta-BA.1 RBD as a booster in mice, shedding light on the antigen design for the next-generation COVID-19 vaccines.

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目前流行的异源嵌合rbd -二聚体mRNA疫苗作为灭活疫苗后加强剂的快速评价
随着严重急性呼吸综合征冠状病毒2型(SARS-CoV-2)的持续突变,奥密克戎亚变种的严重免疫逃逸促使开发下一代广谱疫苗,特别是在中国和许多其他国家灭活疫苗高水平接种覆盖率后,作为加强针。此前,我们基于SARS-CoV-2刺突蛋白的串联同源型受体结合结构域(RBD)-二聚体开发了2019冠状病毒病(新冠肺炎)蛋白亚单位疫苗ZF2001®。我们将抗原升级为异嵌合原型(PT)-β或德尔塔BA.1 RBD二聚体,以扩大交叉保护效力,并通过蛋白质亚单位和mRNA疫苗平台证明其有效性。在此,我们进一步探索了异嵌合RBD二聚体mRNA疫苗,并在小鼠中接种两剂灭活疫苗(IV)后评估了其作为加强针的广谱活性。我们的数据表明,嵌合疫苗显著提高了中和抗体水平和针对变体的特异性T细胞反应,PT-Beta在小鼠中优于Delta-BA.1 RBD作为加强剂,为下一代新冠肺炎疫苗的抗原设计提供了线索。
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来源期刊
Biosafety and Health
Biosafety and Health Medicine-Infectious Diseases
CiteScore
7.60
自引率
0.00%
发文量
116
审稿时长
66 days
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