Research Network of Immunity and Health (RNIH), Beijing Institutes of Life Science, Chinese Academy of Sciences, Beijing 100101, China.
CAS Key Laboratory of Pathogen Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, China.
Cell. 2022 Jun 23;185(13):2265-2278.e14. doi: 10.1016/j.cell.2022.04.029. Epub 2022 Apr 27.
Breakthrough infections by SARS-CoV-2 variants become the global challenge for pandemic control. Previously, we developed the protein subunit vaccine ZF2001 based on the dimeric receptor-binding domain (RBD) of prototype SARS-CoV-2. Here, we developed a chimeric RBD-dimer vaccine approach to adapt SARS-CoV-2 variants. A prototype-Beta chimeric RBD-dimer was first designed to adapt the resistant Beta variant. Compared with its homotypic forms, the chimeric vaccine elicited broader sera neutralization of variants and conferred better protection in mice. The protection of the chimeric vaccine was further verified in macaques. This approach was generalized to develop Delta-Omicron chimeric RBD-dimer to adapt the currently prevalent variants. Again, the chimeric vaccine elicited broader sera neutralization of SARS-CoV-2 variants and conferred better protection against challenge by either Delta or Omicron SARS-CoV-2 in mice. The chimeric approach is applicable for rapid updating of immunogens, and our data supported the use of variant-adapted multivalent vaccine against circulating and emerging variants.
SARS-CoV-2 变异株突破性感染成为全球疫情防控的挑战。此前，我们基于原型 SARS-CoV-2 的二聚体受体结合域（RBD）开发了蛋白亚单位疫苗 ZF2001。在此，我们开发了一种嵌合 RBD-二聚体疫苗方法来适应 SARS-CoV-2 变异株。首先设计了原型-β嵌合 RBD-二聚体来适应具有耐药性的β变异株。与同型相比，嵌合疫苗诱导了更广泛的针对变异株的血清中和作用，并在小鼠中提供了更好的保护作用。嵌合疫苗在猕猴中的保护作用也得到了验证。该方法进一步推广到开发 Delta-Omicron 嵌合 RBD-二聚体以适应目前流行的变异株。同样，嵌合疫苗诱导了更广泛的针对 SARS-CoV-2 变异株的血清中和作用，并在小鼠中提供了更好的针对 Delta 或 Omicron SARS-CoV-2 挑战的保护作用。嵌合方法适用于快速更新免疫原，我们的数据支持使用针对流行和新出现变异株的多价变异适应疫苗。
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