目的  对新型冠状病毒刺突蛋白（spike，S）进行抗原性聚类与基因型聚簇的关联分析，为疫苗设计的方向提供参考。方法  基于476条新型冠状病毒基因，分析S序列的氨基酸进化情况并构建系统发育树。在抗原抗体结合界面提取抗原表位并对序列进行三维空间结构模拟，将提取表位与模拟结构两两配对计算抗原性距离，构建抗原相似性聚类树。通过比较毒株对应的序列系统发育树和抗原相似性聚类树，评估新型冠状病毒进化与抗原性的关系。结果 新型冠状病毒的系统发育树上不同谱系的毒株分别聚在相应的分支上，其中Alpha分支与Gamma分支相距最远，序列相似度最低；同时Omicron株的BA.1到BA.5分支聚在一起，呈现出高度的序列相似性，且与野生型毒株的距离较远。抗原性的聚类表明，Omicron株的5个谱系的抗原性聚集情况与序列聚类情况不一致，并未呈现出较为明显的抗原性聚类。结论  新型冠状病毒S的抗原性聚类与序列聚类情况可能并不一致，而是更倾向于抗原表位的差异。疫苗设计中，考虑抗原性位点差异特征的设计思路将会比基于家族谱系的设计思路更为有效。

Objective  To analyze the association of antigenicity cluster and genotype cluster of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S), to provide reference for vaccine design. Methods  Based on 476 SARS-CoV-2 gene sequences, the evolution of S was analyzed and the phylogenetic tree was constructed. Secondly, the antigen epitopes were extracted from the antigen-antibody binding interface and the 3D spatial structure of the sequences was simulated. The antigenicity distance was calculated by pairing the epitopes with the modeled structure, and the antigen similarity cluster tree was constructed. Finally, the relationship between evolution and antigenicity of SARS-CoV-2 was evaluated by comparing the sequence phylogenetic tree and the antigen similarity cluster tree corresponding to the virus strains. Results  The phylogenetic tree was evenly distributed, and the strains of the same branch clustered together. The Alpha branch and the Gamma branch were the most distant and the least similar. BA.1-BA.5 lineages of Omicron clade were clustered together with high similarity. The antigenicity clustering was different from the phylogenetic tree for 5 Omicron lineages, which indicated the antigenicity cluster was not apparent. Conclusion  The antigenic similarity of S is different from the sequence similarity, and rather rely on the difference between mutant epitopes, which indicated that for vaccine design, difference between antigenic sites is more reliable than the design based on different lineage.