Your browser doesn't support javascript.
loading
Comprehensive Epitope Mapping of Broad Sarbecovirus Neutralizing Antibodies
Yunlong Cao; Ayijiang Yisimayi; Fanchong Jian; Tianhe Xiao; Weiliang Song; Jing Wang; Shuo Du; Zhiying Zhang; Pulan Liu; Xiaohua Hao; Qianqian Li; Xiaosu Chen; Lei Wang; Peng Wang; Ran An; Yao Wang; Jing Wang; Peng Yang; Haiyan Sun; Lijuan Zhao; Wen Zhang; Dong Zhao; Jiang Zheng; Lingling Yu; Can Li; Na Zhang; Rui Wang; Xiao Niu; Sijie Yang; Xuetao Song; Linlin Zheng; Zhiqiang Li; Qingqing Gu; Fei Shao; Weijin Huang; Youchun Wang; Zhongyang Shen; Xiangxi Wang; Ronghua Jin; Junyu Xiao; Xiaoliang Sunney Xie.
Affiliation
  • Yunlong Cao; Changping Laboratory, Beijing, P.R. China.;Biomedical Pioneering Innovation Center (BIOPIC), Peking University, Beijing, P.R. China.;Beijing Advanced Innovation
  • Ayijiang Yisimayi; Biomedical Pioneering Innovation Center (BIOPIC), Peking University, Beijing, P.;School of Life Sciences, Peking University, Beijing, 100871, P.R. China.
  • Fanchong Jian; Biomedical Pioneering Innovation Center (BIOPIC), Peking University, Beijing, P.;College of Chemistry and Molecular Engineering, Peking University, Beijing, P.R
  • Tianhe Xiao; Biomedical Pioneering Innovation Center (BIOPIC), Peking University, Beijing, P.;Joint Graduate Program of Peking-Tsinghua-NIBS, Academy for Advanced Interdisci
  • Weiliang Song; Biomedical Pioneering Innovation Center (BIOPIC), Peking University, Beijing, P.;School of Life Sciences, Peking University, Beijing, 100871, P.R. China.
  • Jing Wang; Biomedical Pioneering Innovation Center (BIOPIC), Peking University, Beijing, P.;School of Life Sciences, Peking University, Beijing, 100871, P.R. China.
  • Shuo Du; School of Life Sciences, Peking University, Beijing, 100871, P.R. China.
  • Zhiying Zhang; School of Life Sciences, Peking University, Beijing, 100871, P.R. China.
  • Pulan Liu; School of Life Sciences, Peking University, Beijing, 100871, P.R. China.
  • Xiaohua Hao; Beijing Ditan Hospital, Capital Medical University, Beijing, P.R. China.
  • Qianqian Li; Division of HIV/AIDS and Sex-transmitted Virus Vaccines, Institute for Biological Product Control, National Institutes for Food and Drug Control (NIFDC), Beijin
  • Xiaosu Chen; Institute for Immunology, College of Life Sciences, Nankai University, Tianjin, P. R. China.
  • Lei Wang; CAS Key Laboratory of Infection and Immunity, National Laboratory of Macromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China
  • Peng Wang; Changping Laboratory, Beijing, P.R. China.
  • Ran An; Biomedical Pioneering Innovation Center (BIOPIC), Peking University, Beijing, P.R. China.
  • Yao Wang; Changping Laboratory, Beijing, P.R. China.
  • Jing Wang; Changping Laboratory, Beijing, P.R. China.
  • Peng Yang; CAS Key Laboratory of Infection and Immunity, National Laboratory of Macromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China
  • Haiyan Sun; Changping Laboratory, Beijing, P.R. China.
  • Lijuan Zhao; Changping Laboratory, Beijing, P.R. China.2Biomedical Pioneering Innovation Center (BIOPIC), Peking University, Beijing, P.R. China.;Beijing Advanced Innovation
  • Wen Zhang; Beijing Ditan Hospital, Capital Medical University
  • Dong Zhao; Beijing Ditan Hospital, Capital Medical University
  • Jiang Zheng; Changping Laboratory, Beijing, P.R. China.
  • Lingling Yu; Changping Laboratory, Beijing, P.R. China.
  • Can Li; Changping Laboratory, Beijing, P.R. China.
  • Na Zhang; Changping Laboratory, Beijing, P.R. China.
  • Rui Wang; Changping Laboratory, Beijing, P.R. China.
  • Xiao Niu; Biomedical Pioneering Innovation Center (BIOPIC), Peking University, Beijing, P.R. China.
  • Sijie Yang; Biomedical Pioneering Innovation Center (BIOPIC), Peking University, Beijing, P.R. China.Tsinghua-Peking Center for Life Sciences, Tsinghua University, Beijing,
  • Xuetao Song; Changping Laboratory, Beijing, P.R. China.
  • Linlin Zheng; Changping Laboratory, Beijing, P.R. China.
  • Zhiqiang Li; Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, 100871, P.R. China;Peking-Tsinghua Center for Life Sciences, Peking University, Beij
  • Qingqing Gu; Changping Laboratory, Beijing, P.R. China.
  • Fei Shao; Changping Laboratory, Beijing, P.R. China.
  • Weijin Huang; Division of HIV/AIDS and Sex-transmitted Virus Vaccines, Institute for Biological Product Control, National Institutes for Food and Drug Control (NIFDC) and WHO
  • Youchun Wang; Division of HIV/AIDS and Sex-transmitted Virus Vaccines, Institute for Biological Product Control, National Institutes for Food and Drug Control (NIFDC) and WHO
  • Zhongyang Shen; Organ Transplant Center, NHC Key Laboratory for Critical Care Medicine, Tianjin First Central Hospital, Nankai University, Tianjin, P. R. China.
  • Xiangxi Wang; CAS Key Laboratory of Infection and Immunity, National Laboratory of Macromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China
  • Ronghua Jin; Beijing Ditan Hospital, Capital Medical University, Beijing, P.R. China.
  • Junyu Xiao; School of Life Sciences, Peking University, Beijing, 100871, P.R. China.;Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, 100871, P.R
  • Xiaoliang Sunney Xie; Changping Laboratory, Beijing, P.R. China.2Biomedical Pioneering Innovation Center (BIOPIC), Peking University, Beijing, P.R. China.;Beijing Advanced Innovation
Preprint in English | bioRxiv | ID: ppbiorxiv-479349
ABSTRACT
Omicron sub-lineage BA.2 has rapidly surged globally, accounting for over 60% of recent SARS-CoV-2 infections. Newly acquired RBD mutations and high transmission advantage over BA.1 urge the investigation of BA.2s immune evasion capability. Here, we show that BA.2 causes strong neutralization resistance, comparable to BA.1, in vaccinated individuals plasma. However, BA.2 displays more severe antibody evasion in BA.1 convalescents, and most prominently, in vaccinated SARS convalescents plasma, suggesting a substantial antigenicity difference between BA.2 and BA.1. To specify, we determined the escaping mutation profiles1,2 of 714 SARS-CoV-2 RBD neutralizing antibodies, including 241 broad sarbecovirus neutralizing antibodies isolated from SARS convalescents, and measured their neutralization efficacy against BA.1, BA.1.1, BA.2. Importantly, BA.2 specifically induces large-scale escape of BA.1/BA.1.1-effective broad sarbecovirus neutralizing antibodies via novel mutations T376A, D405N, and R408S. These sites were highly conserved across sarbecoviruses, suggesting that Omicron BA.2 arose from immune pressure selection instead of zoonotic spillover. Moreover, BA.2 reduces the efficacy of S309 (Sotrovimab)3,4 and broad sarbecovirus neutralizing antibodies targeting the similar epitope region, including BD55-5840. Structural comparisons of BD55-5840 in complexes with BA.1 and BA.2 spike suggest that BA.2 could hinder antibody binding through S371F-induced N343-glycan displacement. Intriguingly, the absence of G446S mutation in BA.2 enabled a proportion of 440-449 linear epitope targeting antibodies to retain neutralizing efficacy, including COV2-2130 (Cilgavimab)5. Together, we showed that BA.2 exhibits distinct antigenicity compared to BA.1 and provided a comprehensive profile of SARS-CoV-2 antibody escaping mutations. Our study offers critical insights into the humoral immune evading mechanism of current and future variants.
License
cc_by_nc_nd
Full text: Available Collection: Preprints Database: bioRxiv Language: English Year: 2022 Document type: Preprint
Full text: Available Collection: Preprints Database: bioRxiv Language: English Year: 2022 Document type: Preprint
...