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
Copyright © 2024. Published by Elsevier Inc..
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).
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - year:2024 |
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| Enthalten in: |
Med (New York, N.Y.) - (2024) vom: 28. März |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
He, Qingwen [VerfasserIn] |
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| Links: |
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| Themen: |
BA.2.86 |
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| Anmerkungen: |
Date Revised 04.04.2024 published: Print-Electronic ClinicalTrials.gov: NCT05850507 Citation Status Publisher |
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| doi: |
10.1016/j.medj.2024.03.006 |
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| funding: |
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NLM37064154X |
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| 100 | 1 | |a He, Qingwen |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a 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 |
| 264 | 1 | |c 2024 | |
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| 500 | |a Date Revised 04.04.2024 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a ClinicalTrials.gov: NCT05850507 | ||
| 500 | |a Citation Status Publisher | ||
| 520 | |a Copyright © 2024. Published by Elsevier Inc. | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a 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) | ||
| 650 | 4 | |a Journal Article | |
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| 650 | 4 | |a EG.5.1 | |
| 650 | 4 | |a JN.1 | |
| 650 | 4 | |a RBD-dimer | |
| 650 | 4 | |a SARS-CoV-2 | |
| 650 | 4 | |a Translation to humans | |
| 650 | 4 | |a ZF2001 vaccine | |
| 650 | 4 | |a ZF2202-A | |
| 650 | 4 | |a immune evasion | |
| 650 | 4 | |a neutralizing antibody | |
| 700 | 1 | |a An, Yaling |e verfasserin |4 aut | |
| 700 | 1 | |a Zhou, Xuemei |e verfasserin |4 aut | |
| 700 | 1 | |a Xie, Haitang |e verfasserin |4 aut | |
| 700 | 1 | |a Tao, Lifeng |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Dedong |e verfasserin |4 aut | |
| 700 | 1 | |a Zheng, Anqi |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Linjie |e verfasserin |4 aut | |
| 700 | 1 | |a Xu, Zepeng |e verfasserin |4 aut | |
| 700 | 1 | |a Yu, Shufan |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Ruyue |e verfasserin |4 aut | |
| 700 | 1 | |a Hu, Hua |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Kefang |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Qihui |e verfasserin |4 aut | |
| 700 | 1 | |a Dai, Lianpan |e verfasserin |4 aut | |
| 700 | 1 | |a Xu, Kun |e verfasserin |4 aut | |
| 700 | 1 | |a Gao, George F |e verfasserin |4 aut | |
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