Neutralization of EG.5, EG.5.1, BA.2.86, and JN.1 by antisera from dimeric receptor-binding domain subunit vaccines and 41 human monoclonal antibodies

Qingwen He; Yaling An; Xuemei Zhou; Haitang Xie; Lifeng Tao; Dedong Li; Anqi Zheng; Linjie Li; Zepeng Xu; Shufan Yu; Ruyue Wang; Hua Hu; Kefang Liu; Qihui Wang; Lianpan Dai; Kun Xu; George F Gao

doi:10.1016/j.medj.2024.03.006

Neutralization of EG.5, EG.5.1, BA.2.86, and JN.1 by antisera from dimeric receptor-binding domain subunit vaccines and 41 human monoclonal antibodies

Med. 2024 Mar 28:S2666-6340(24)00118-1. doi: 10.1016/j.medj.2024.03.006. Online ahead of print.

Authors

Qingwen He¹, Yaling An², Xuemei Zhou³, Haitang Xie⁴, Lifeng Tao⁵, Dedong Li², Anqi Zheng², Linjie Li², Zepeng Xu⁶, Shufan Yu², Ruyue Wang⁵, Hua Hu⁴, Kefang Liu², Qihui Wang², Lianpan Dai², Kun Xu⁷, George F Gao⁸

Affiliations

¹ Department of Microbiology, School of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, China; CAS Key Laboratory of Pathogen Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences (CAS), Beijing, China.
² CAS Key Laboratory of Pathogen Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences (CAS), Beijing, China.
³ CAS Key Laboratory of Pathogen Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences (CAS), Beijing, China; School of Life Sciences, Hebei University, Baoding, Hebei Province, China.
⁴ Yijishan Hospital of Wannan Medical College, Wuhu, Anhui Province, China.
⁵ Anhui Zhifei Longcom Biopharmaceutical Co., Ltd., Hefei, Anhui Province, China.
⁶ CAS Key Laboratory of Pathogen Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences (CAS), Beijing, China; Faculty of Health Sciences, University of Macau, Macau SAR, China.
⁷ Research Network of Immunity and Health (RNIH), Beijing Institutes of Life Science, Chinese Academy of Sciences (CAS), Beijing, China. Electronic address: xukun@biols.ac.cn.
⁸ Department of Microbiology, School of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, China; CAS Key Laboratory of Pathogen Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences (CAS), Beijing, China; Research Network of Immunity and Health (RNIH), Beijing Institutes of Life Science, Chinese Academy of Sciences (CAS), Beijing, China; D. H. Chen School of Universal Health and School of Public Health, Zhejiang University, Hangzhou, Zhejiang Province, China. Electronic address: gfgao@zju.edu.cn.

PMID: 38574739
DOI: 10.1016/j.medj.2024.03.006

Abstract

Background: The recently circulating Omicron variants BA.2.86 and JN.1 were identified with more than 30 amino acid changes on the spike protein compared to BA.2 or XBB.1.5. This study aimed to comprehensively assess the immune escape potential of BA.2.86, JN.1, EG.5, and EG.5.1.

Methods: We collected human and murine sera to evaluate serological neutralization activities. The participants received three doses of coronavirus disease 2019 (COVID-19) vaccines or a booster dose of the ZF2022-A vaccine (Delta-BA.5 receptor-binding domain [RBD]-heterodimer immunogen) or experienced a breakthrough infection (BTI). The ZF2202-A vaccine is under clinical trial study (ClinicalTrials.gov: NCT05850507). BALB/c mice were vaccinated with a panel of severe acute respiratory syndrome coronavirus 2 RBD-dimer proteins. The antibody evasion properties of these variants were analyzed with 41 representative human monoclonal antibodies targeting the eight RBD epitopes.

Findings: We found that BA.2.86 had less neutralization evasion than EG.5 and EG.5.1 in humans. The ZF2202-A booster induced significantly higher neutralizing titers than BTI. Furthermore, BA.2.86 and JN.1 exhibited stronger antibody evasion than EG.5 and EG.5.1 on RBD-4 and RBD-5 epitopes. Compared to BA.2.86, JN.1 further lost the ability to bind to several RBD-1 monoclonal antibodies and displayed further immune escape.

Conclusions: Our data showed that the currently dominating sub-variant, JN.1, showed increased immune evasion compared to BA.2.86 and EG.5.1, which is highly concerning. This study provides a timely risk assessment of the interested sub-variants and the basis for updating COVID-19 vaccines.

Funding: This work was funded by the National Key R&D Program of China, the National Natural Science Foundation of China, the Beijing Life Science Academy, the Bill & Melinda Gates Foundation, and the Postdoctoral Fellowship Program of China Postdoctoral Science Foundation (CPSF).

Keywords: BA.2.86; EG.5; EG.5.1; JN.1; RBD-dimer; SARS-CoV-2; Translation to humans; ZF2001 vaccine; ZF2202-A; immune evasion; neutralizing antibody.

Associated data

ClinicalTrials.gov/NCT05850507