Comparative Analysis of Host Cell Entry Efficiency and Neutralization Sensitivity of Emerging SARS-CoV-2 Lineages KP.2, KP.2.3, KP.3, and LB.1
New SARS-CoV-2 lineages continue to evolve and may exhibit new characteristics regarding host cell entry efficiency and potential for antibody evasion. Here, employing pseudotyped particles, we compared the host cell entry efficiency, ACE2 receptor usage, and sensitivity to antibody-mediated neutral...
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MDPI AG
2024-10-01
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| Series: | Vaccines |
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| Online Access: | https://www.mdpi.com/2076-393X/12/11/1236 |
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| author | Nianzhen Chen Katharina Emma Decker Sebastian R. Schulz Amy Kempf Inga Nehlmeier Anna-Sophie Moldenhauer Alexandra Dopfer-Jablonka Georg M. N. Behrens Metodi V. Stankov Luis Manthey Hans-Martin Jäck Markus Hoffmann Stefan Pöhlmann Prerna Arora |
| author_facet | Nianzhen Chen Katharina Emma Decker Sebastian R. Schulz Amy Kempf Inga Nehlmeier Anna-Sophie Moldenhauer Alexandra Dopfer-Jablonka Georg M. N. Behrens Metodi V. Stankov Luis Manthey Hans-Martin Jäck Markus Hoffmann Stefan Pöhlmann Prerna Arora |
| author_sort | Nianzhen Chen |
| collection | DOAJ |
| description | New SARS-CoV-2 lineages continue to evolve and may exhibit new characteristics regarding host cell entry efficiency and potential for antibody evasion. Here, employing pseudotyped particles, we compared the host cell entry efficiency, ACE2 receptor usage, and sensitivity to antibody-mediated neutralization of four emerging SARS-CoV-2 lineages, KP.2, KP.2.3, KP.3, and LB.1. The XBB.1.5 and JN.1 lineages served as controls. Our findings reveal that KP.2, KP.2.3, KP.3, and LB.1 lineages enter host cells efficiently and in an ACE2-dependent manner, and that KP.3 is more adept at entering Calu-3 lung cells than JN.1. However, the variants differed in their capacity to employ ACE2 orthologues from animal species for entry, suggesting differences in ACE2 interactions. Moreover, we demonstrate that only two out of seven therapeutic monoclonal antibody (mAbs) in preclinical development retain robust neutralizing activity against the emerging JN.1 sublineages tested, while three mAbs displayed strongly reduced neutralizing activity and two mAbs lacked neutralizing activity against any of the lineages tested. Furthermore, our results show that KP.2, KP.2.3, KP.3, and LB.1 lineages evade neutralization by antibodies induced by infection or vaccination with greater efficiency than JN.1, particularly in individuals without hybrid immunity. This study indicates that KP.2, KP.2.3, KP.3, and LB.1 differ in ACE2 interactions and the efficiency of lung cell entry and suggest that evasion of neutralizing antibodies drove the emergence of these variants. |
| format | Article |
| id | doaj-art-0c55e3d4b4ff40df90a59f5934cc15f5 |
| institution | OA Journals |
| issn | 2076-393X |
| language | English |
| publishDate | 2024-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Vaccines |
| spelling | doaj-art-0c55e3d4b4ff40df90a59f5934cc15f52025-08-20T02:27:40ZengMDPI AGVaccines2076-393X2024-10-011211123610.3390/vaccines12111236Comparative Analysis of Host Cell Entry Efficiency and Neutralization Sensitivity of Emerging SARS-CoV-2 Lineages KP.2, KP.2.3, KP.3, and LB.1Nianzhen Chen0Katharina Emma Decker1Sebastian R. Schulz2Amy Kempf3Inga Nehlmeier4Anna-Sophie Moldenhauer5Alexandra Dopfer-Jablonka6Georg M. N. Behrens7Metodi V. Stankov8Luis Manthey9Hans-Martin Jäck10Markus Hoffmann11Stefan Pöhlmann12Prerna Arora13Infection Biology Unit, German Primate Center—Leibniz Institute for Primate Research, 37077 Göttingen, GermanyInfection Biology Unit, German Primate Center—Leibniz Institute for Primate Research, 37077 Göttingen, GermanyDivision of Molecular Immunology, Department of Internal Medicine 3, Friedrich-Alexander University of Erlangen-Nürnberg, 91054 Erlangen, GermanyInfection Biology Unit, German Primate Center—Leibniz Institute for Primate Research, 37077 Göttingen, GermanyInfection Biology Unit, German Primate Center—Leibniz Institute for Primate Research, 37077 Göttingen, GermanyInfection Biology Unit, German Primate Center—Leibniz Institute for Primate Research, 37077 Göttingen, GermanyDepartment of Rheumatology and Immunology, Hannover Medical School, 30625 Hannover, GermanyDepartment of Rheumatology and Immunology, Hannover Medical School, 30625 Hannover, GermanyDepartment of Rheumatology and Immunology, Hannover Medical School, 30625 Hannover, GermanyDepartment of Rheumatology and Immunology, Hannover Medical School, 30625 Hannover, GermanyDivision of Molecular Immunology, Department of Internal Medicine 3, Friedrich-Alexander University of Erlangen-Nürnberg, 91054 Erlangen, GermanyInfection Biology Unit, German Primate Center—Leibniz Institute for Primate Research, 37077 Göttingen, GermanyInfection Biology Unit, German Primate Center—Leibniz Institute for Primate Research, 37077 Göttingen, GermanyInfection Biology Unit, German Primate Center—Leibniz Institute for Primate Research, 37077 Göttingen, GermanyNew SARS-CoV-2 lineages continue to evolve and may exhibit new characteristics regarding host cell entry efficiency and potential for antibody evasion. Here, employing pseudotyped particles, we compared the host cell entry efficiency, ACE2 receptor usage, and sensitivity to antibody-mediated neutralization of four emerging SARS-CoV-2 lineages, KP.2, KP.2.3, KP.3, and LB.1. The XBB.1.5 and JN.1 lineages served as controls. Our findings reveal that KP.2, KP.2.3, KP.3, and LB.1 lineages enter host cells efficiently and in an ACE2-dependent manner, and that KP.3 is more adept at entering Calu-3 lung cells than JN.1. However, the variants differed in their capacity to employ ACE2 orthologues from animal species for entry, suggesting differences in ACE2 interactions. Moreover, we demonstrate that only two out of seven therapeutic monoclonal antibody (mAbs) in preclinical development retain robust neutralizing activity against the emerging JN.1 sublineages tested, while three mAbs displayed strongly reduced neutralizing activity and two mAbs lacked neutralizing activity against any of the lineages tested. Furthermore, our results show that KP.2, KP.2.3, KP.3, and LB.1 lineages evade neutralization by antibodies induced by infection or vaccination with greater efficiency than JN.1, particularly in individuals without hybrid immunity. This study indicates that KP.2, KP.2.3, KP.3, and LB.1 differ in ACE2 interactions and the efficiency of lung cell entry and suggest that evasion of neutralizing antibodies drove the emergence of these variants.https://www.mdpi.com/2076-393X/12/11/1236SARS-CoV-2 lineagesACE2 receptor interactionsantibody evasion |
| spellingShingle | Nianzhen Chen Katharina Emma Decker Sebastian R. Schulz Amy Kempf Inga Nehlmeier Anna-Sophie Moldenhauer Alexandra Dopfer-Jablonka Georg M. N. Behrens Metodi V. Stankov Luis Manthey Hans-Martin Jäck Markus Hoffmann Stefan Pöhlmann Prerna Arora Comparative Analysis of Host Cell Entry Efficiency and Neutralization Sensitivity of Emerging SARS-CoV-2 Lineages KP.2, KP.2.3, KP.3, and LB.1 Vaccines SARS-CoV-2 lineages ACE2 receptor interactions antibody evasion |
| title | Comparative Analysis of Host Cell Entry Efficiency and Neutralization Sensitivity of Emerging SARS-CoV-2 Lineages KP.2, KP.2.3, KP.3, and LB.1 |
| title_full | Comparative Analysis of Host Cell Entry Efficiency and Neutralization Sensitivity of Emerging SARS-CoV-2 Lineages KP.2, KP.2.3, KP.3, and LB.1 |
| title_fullStr | Comparative Analysis of Host Cell Entry Efficiency and Neutralization Sensitivity of Emerging SARS-CoV-2 Lineages KP.2, KP.2.3, KP.3, and LB.1 |
| title_full_unstemmed | Comparative Analysis of Host Cell Entry Efficiency and Neutralization Sensitivity of Emerging SARS-CoV-2 Lineages KP.2, KP.2.3, KP.3, and LB.1 |
| title_short | Comparative Analysis of Host Cell Entry Efficiency and Neutralization Sensitivity of Emerging SARS-CoV-2 Lineages KP.2, KP.2.3, KP.3, and LB.1 |
| title_sort | comparative analysis of host cell entry efficiency and neutralization sensitivity of emerging sars cov 2 lineages kp 2 kp 2 3 kp 3 and lb 1 |
| topic | SARS-CoV-2 lineages ACE2 receptor interactions antibody evasion |
| url | https://www.mdpi.com/2076-393X/12/11/1236 |
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