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BA.2.12.1, BA.4 and BA.5 escape antibodies elicited by Omicron infection
Yunlong Richard Cao; Ayijiang Yisimayi; Fanchong Jian; Weiliang Song; Tianhe Xiao; Lei Wang; Shuo Du; Jing Wang; Qianqian Li; Xiaosu Chen; Yuanling Yu; Peng Wang; Zhiying Zhang; Pulan Liu; Ran An; Xiaohua Hao; Yao Wang; Jing Wang; Rui Feng; Haiyan Sun; Lijuan Zhao; Wen Zhang; Dong Zhao; Jiang Zheng; Lingling Yu; Can Li; Na Zhang; Rui Wang; Xiao Niu; Sijie Yang; Xuetao Song; Yangyang Chai; Ye Hu; Yansong Shi; Linlin Zheng; Zhiqiang Li; Qingqing Gu; Fei Shao; Weijin Huang; Ronghua Jin; Zhongyang Shen; Youchun Wang; Xiangxi Wang; Junyu Xiao; Xiaoliang Sunney Xie.
Affiliation
  • Yunlong Richard Cao; Biomedical Pioneering Innovation Center (BIOPIC), Peking University
  • Ayijiang Yisimayi; Biomedical Pioneering Innovation Center (BIOPIC), Peking University
  • Fanchong Jian; Biomedical Pioneering Innovation Center (BIOPIC), Peking University
  • Weiliang Song; Biomedical Pioneering Innovation Center (BIOPIC), Peking University
  • Tianhe Xiao; Biomedical Pioneering Innovation Center (BIOPIC), Peking University
  • Lei Wang; CAS Key Laboratory of Infection and Immunity, National Laboratory of Macromolecules, Institute of Biophysics, Chinese Academy of Sciences
  • Shuo Du; School of Life Sciences, Peking University
  • Jing Wang; Biomedical Pioneering Innovation Center (BIOPIC), Peking University
  • Qianqian Li; Division of HIV/AIDS and Sex-transmitted Virus Vaccines, Institute for Biological Product Control, National Institutes for Food and Drug Control (NIFDC)
  • Xiaosu Chen; Institute for Immunology, College of Life Sciences, Nankai University
  • Yuanling Yu; Division of HIV/AIDS and Sex-transmitted Virus Vaccines, Institute for Biological Product Control, National Institutes for Food and Drug Control (NIFDC), Beijin
  • Peng Wang; Changping Laboratory
  • Zhiying Zhang; School of Life Sciences, Peking University
  • Pulan Liu; School of Life Sciences, Peking University
  • Ran An; Biomedical Pioneering Innovation Center (BIOPIC), Peking University
  • Xiaohua Hao; Beijing Ditan Hospital, Capital Medical University
  • Yao Wang; Changping Laboratory
  • Jing Wang; Changping Laboratory
  • Rui Feng; CAS Key Laboratory of Infection and Immunity, National Laboratory of Macromolecules, Institute of Biophysics, Chinese Academy of Sciences
  • Haiyan Sun; Changping Laboratory
  • Lijuan Zhao; Changping Laboratory
  • Wen Zhang; Beijing Ditan Hospital, Capital Medical University
  • Dong Zhao; Beijing Ditan Hospital, Capital Medical University
  • Jiang Zheng; Changping Laboratory
  • Lingling Yu; Changping Laboratory
  • Can Li; Changping Laboratory
  • Na Zhang; Changping Laboratory
  • Rui Wang; Changping Laboratory
  • Xiao Niu; Biomedical Pioneering Innovation Center (BIOPIC), Peking University
  • Sijie Yang; Biomedical Pioneering Innovation Center (BIOPIC), Peking University
  • Xuetao Song; Changping Laboratory
  • Yangyang Chai; Institute for Immunology, College of Life Sciences, Nankai University
  • Ye Hu; Institute for Immunology, College of Life Sciences, Nankai University
  • Yansong Shi; Institute for Immunology, College of Life Sciences, Nankai University
  • Linlin Zheng; Changping Laboratory
  • Zhiqiang Li; Peking-Tsinghua Center for Life Sciences, Peking University
  • Qingqing Gu; Changping Laboratory
  • Fei Shao; Changping Laboratory
  • Weijin Huang; Division of HIV/AIDS and Sex-transmitted Virus Vaccines, Institute for Biological Product Control, National Institutes for Food and Drug Control (NIFDC)
  • Ronghua Jin; Beijing Ditan Hospital, Capital Medical University
  • Zhongyang Shen; Organ Transplant Center, NHC Key Laboratory for Critical Care Medicine, Tianjin First Central Hospital, Nankai University
  • Youchun Wang; Division of HIV/AIDS and Sex-transmitted Virus Vaccines, Institute for Biological Product Control, National Institutes for Food and Drug Control (NIFDC)
  • Xiangxi Wang; CAS Key Laboratory of Infection and Immunity, National Laboratory of Macromolecules, Institute of Biophysics, Chinese Academy of Sciences
  • Junyu Xiao; School of Life Sciences, Peking University
  • Xiaoliang Sunney Xie; Biomedical Pioneering Innovation Center (BIOPIC), Peking University
Preprint in English | bioRxiv | ID: ppbiorxiv-489997
ABSTRACT
SARS-CoV-2 Omicron sublineages BA.2.12.1, BA.4 and BA.5 exhibit higher transmissibility over BA.21. The new variants receptor binding and immune evasion capability require immediate investigation. Here, coupled with Spike structural comparisons, we show that BA.2.12.1 and BA.4/BA.5 exhibit comparable ACE2-binding affinities to BA.2. Importantly, BA.2.12.1 and BA.4/BA.5 display stronger neutralization evasion than BA.2 against the plasma from 3-dose vaccination and, most strikingly, from post-vaccination BA.1 infections. To delineate the underlying antibody evasion mechanism, we determined the escaping mutation profiles2, epitope distribution3 and Omicron neutralization efficacy of 1640 RBD-directed neutralizing antibodies (NAbs), including 614 isolated from BA.1 convalescents. Interestingly, post-vaccination BA.1 infection mainly recalls wildtype-induced humoral memory. The resulting elicited antibodies could neutralize both wildtype and BA.1 and are enriched on non-ACE2-competing epitopes. However, most of these cross-reactive NAbs are heavily escaped by L452Q, L452R and F486V. BA.1 infection can also induce new clones of BA.1-specific antibodies that potently neutralize BA.1; nevertheless, these NAbs are largely escaped by BA.2/BA.4/BA.5 due to D405N and F486V, and react weakly to pre-Omicron variants, exhibiting poor neutralization breadths. As for therapeutic NAbs, Bebtelovimab4 and Cilgavimab5 can effectively neutralize BA.2.12.1 and BA.4/BA.5, while the S371F, D405N and R408S mutations would undermine most broad sarbecovirus NAbs. Together, our results indicate that Omicron may evolve mutations to evade the humoral immunity elicited by BA.1 infection, suggesting that BA.1-derived vaccine boosters may not achieve broad-spectrum protection against new Omicron variants.
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Full text: Available Collection: Preprints Database: bioRxiv Type of study: Rct Language: English Year: 2022 Document type: Preprint
Full text: Available Collection: Preprints Database: bioRxiv Type of study: Rct Language: English Year: 2022 Document type: Preprint
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