Cui Lingyan, Li Tingting, Lan Miaolin, Zhou Ming, Xue Wenhui, Zhang Sibo, Wang Hong, Hong Minqing, Zhang Yali, Yuan Lunzhi, Sun Hui, Ye Jianghui, Zheng Qingbing, Guan Yi, Gu Ying, Xia Ningshao, Li Shaowei
State Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, School of Public Health, School of Life Sciences, Xiamen University, Xiamen 361102, China.
National Institute of Diagnostics and Vaccine Development in Infectious Diseases, State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, Collaborative Innovation Center of Biologic Products, National Innovation Platform for Industry-Education Integration in Vaccine Research, the Research Unit of Frontier Technology of Structural Vaccinology of Chinese Academy of Medical Sciences, Xiamen University, Xiamen 361102, China.
iScience. 2024 Jun 11;27(7):110208. doi: 10.1016/j.isci.2024.110208. eCollection 2024 Jul 19.
The emergence of SARS-CoV-2 variants raises concerns about the efficacy of existing COVID-19 vaccines and therapeutics. Previously, we identified a conserved cryptic class 5 epitope of SARS-CoV-2 receptor binding domain (RBD) by two cross-neutralizing antibodies 7D6 and 6D6. Intriguingly, this site remains resistant to substantial mutations occurred in ever-changing SARS-CoV-2 subvariants. As compared to class 3 antibody S309, 6D6 maintains broad and consistent neutralizing activities against SARS-CoV-2 variants. Furthermore, 6D6 effectively protected hamster from the virulent Beta strain. Sequence alignment of approximately 6 million documented SARS-CoV-2 isolates revealed that 6D6 epitope maintains an exceptionally high conservation rate (99.92%). Structural analysis demonstrated that all 33 mutations accumulated in XBB.1.5 since the original strain do not perturb the binding 6D6 to RBD, in line with the sequence analysis throughout the antigenicity evolution of SARS-CoV-2. These findings suggest the potential of this epitope serving as a critical determinant for vaccines and therapeutic design.
严重急性呼吸综合征冠状病毒2（SARS-CoV-2）变体的出现引发了人们对现有新冠病毒疫苗和治疗方法疗效的担忧。此前，我们通过两种交叉中和抗体7D6和6D6鉴定出了SARS-CoV-2受体结合域（RBD）一个保守的隐秘5类表位。有趣的是，该位点对不断变化的SARS-CoV-2亚变体中发生的大量突变仍具有抗性。与3类抗体S309相比，6D6对SARS-CoV-2变体保持广泛且一致的中和活性。此外，6D6有效地保护仓鼠免受毒性强的贝塔毒株感染。对约600万份有记录的SARS-CoV-2分离株进行序列比对后发现，6D6表位的保守率异常高（99.92%）。结构分析表明，自原始毒株以来在XBB.1.5中积累的所有33个突变均未干扰6D6与RBD的结合，这与SARS-CoV-2抗原性演变过程中的序列分析结果一致。这些发现表明该表位有可能作为疫苗和治疗设计的关键决定因素。
