SARS-CoV-2 serotyping based on spike antigenicity and its implications for host immune evasion

作者：Wenjing Ruan, Pengyue Gao, Xiao Qu, Junlan Jiang, Zhennan Zhao, Shitong Qiao, He Zhang, Ting Yang, Dedong Li, Pei Du, Xuancheng Lu, Qihui Wang, Xin Zhao, George F. Gao · 发表于：EBioMedicine · 年份：2025 · DOI：10.1016/j.ebiom.2025.105634 · 被引用次数：12 · 研究领域：SARS-CoV-2 and COVID-19 Research、vaccines and immunoinformatics approaches、COVID-19 Clinical Research Studies

BACKGROUND: As SARS-CoV-2 continues to spread and evolve, new variants/sub-variants emerge, raising concerns about vaccine-induced immune escape. Here, we conducted a systematic analysis of the serology and immunogenicity of major circulating variants/sub-variants of SARS-CoV-2 since the outbreak. METHODS: We expressed and purified trimeric S proteins from 21 SARS-CoV-2 variants, with SARS-CoV included as an outgroup. Mice were immunized, and the resulting antisera were tested for binding antibodies after the third dose injection, and for neutralizing antibodies (NAbs) after both the second and third doses. Using pseudovirus neutralization assays, we evaluated cross-neutralization among major circulating variants. By integrating serological classification, antigenic mapping, and 3D landscape analysis, we explored the antigenic relationships among different SARS-CoV-2 variants and their impact on serological responses. FINDINGS: Based on the cross-neutralization activities of the sera from different S protein vaccinations and antigenicity analyses, we grouped the 21 lineages into six serotypes. Particularly, BA.2.86 and JN.1 had very weak cross-neutralization with all other SARS-CoV-2 sub-variants tested and were grouped into a separate serotype, Serotype VI. INTERPRETATION: This systematic study contributes to a better understanding of the evolution of SARS-CoV-2 and its antigenic characteristics and provides valuable insights for vaccine development. FUNDING: This study was ...