iScience (Jul 2024)
A cryptic site in class 5 epitope of SARS-CoV-2 RBD maintains highly conservation across natural isolates
- Lingyan Cui,
- Tingting Li,
- Miaolin Lan,
- Ming Zhou,
- Wenhui Xue,
- Sibo Zhang,
- Hong Wang,
- Minqing Hong,
- Yali Zhang,
- Lunzhi Yuan,
- Hui Sun,
- Jianghui Ye,
- Qingbing Zheng,
- Yi Guan,
- Ying Gu,
- Ningshao Xia,
- Shaowei Li
Affiliations
- Lingyan Cui
- 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
- Tingting Li
- 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; Corresponding author
- Miaolin Lan
- 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
- Ming Zhou
- 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
- Wenhui Xue
- 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
- Sibo Zhang
- 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
- Hong Wang
- 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
- Minqing Hong
- 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
- Yali Zhang
- 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
- Lunzhi Yuan
- 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
- Hui Sun
- 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
- Jianghui Ye
- 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
- Qingbing Zheng
- 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
- Yi Guan
- State Key Laboratory of Emerging Infectious Diseases, The University of Hong Kong, Hong Kong 999077, China; Joint Institute of Virology (Shantou University and University of Hong Kong), Guangdong-Hongkong Joint Laboratory of Emerging Infectious Diseases, Shantou University, Shantou 515063, China
- Ying Gu
- 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; Corresponding author
- Ningshao Xia
- 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
- Shaowei Li
- 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; Corresponding author
- Journal volume & issue
-
Vol. 27,
no. 7
p. 110208
Abstract
Summary: 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.
