Omicron-specific ultra-potent SARS-CoV-2 neutralizing antibodies targeting the N1/N2 loop of Spike N-terminal domain DOI
Xiaofeng Niu, Zhiqiang Li, Jing Wang

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: July 10, 2024

Abstract A multitude of functional mutations continue to emerge on the N-terminal domain (NTD) spike protein in SARS-CoV-2 Omicron subvariants. Understanding immunogenicity NTD and properties antibodies elicited by it is crucial for comprehending impact viral fitness guiding vaccine design. In this study, we find that most NTD-targeting isolated from individuals with BA.5/BF.7 breakthrough infection (BTI) are ancestral (wildtype or WT)-reactive non-neutralizing. Surprisingly, identified five ultra-potent neutralizing (NAbs) can only bind but not WT NTD. Structural analysis revealed they a unique epitope N1/N2 loop interact receptor-binding (RBD) via light chain. These Omicron-specific NAbs achieve neutralization through ACE2 competition blockage ACE2-mediated S1 shedding. However, BA.2.86 BA.2.87.1, which carry insertions deletions loop, evade these antibodies. Together, provided detailed map antibody repertoire post-Omicron era, demonstrating their vulnerability enabled its evolutionary flexibility, despite potent neutralization. results highlighted importance considering Author Summary COVID-19 pandemic caused severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues be major global public health concern four years after emergence. The critical component glycoprotein, pivotal cellular entry serves as primary target therapeutics development. Characterizing sublineages understanding evolution Here, show vaccination induces majorly non-neutralizing Still, class specifically sublineages. neutralize virus competing blocking analyses reveal NTD, intriguingly glycoprotein. This special binding pattern, escaped BA.2.87.1 sublineages, shedding role recently emerged Our findings provide fresh insights into highlighting capacity evasion due flexibility. underscores carefully

Language: Английский

Distinct patterns of SARS-CoV-2 BA.2.87.1 and JN.1 variants in immune evasion, antigenicity, and cell-cell fusion DOI Creative Commons

Pei Li,

Yajie Liu, Julia N. Faraone

et al.

mBio, Journal Year: 2024, Volume and Issue: 15(5)

Published: April 9, 2024

The rapid evolution of SARS-CoV-2 variants presents a constant challenge to the global vaccination effort. In this study, we conducted comprehensive investigation into two newly emerged variants, BA.2.87.1 and JN.1, focusing on their neutralization resistance, infectivity, antigenicity, cell-cell fusion, spike processing. Neutralizing antibody (nAb) titers were assessed in diverse cohorts, including individuals who received bivalent mRNA vaccine booster, patients infected during BA.2.86/JN.1-wave, hamsters vaccinated with XBB.1.5-monovalent vaccine. We found that shows much less nAb escape from WT-BA.4/5 JN.1-wave breakthrough infection sera compared JN.1 XBB.1.5. Interestingly, is more resistant by XBB.1.5-monovalent-vaccinated hamster than BA.2.86/JN.1 XBB.1.5, but efficiently neutralized class III monoclonal S309, which largely fails neutralize BA.2.86/JN.1. Importantly, exhibits higher levels fusion activity, furin cleavage efficiency Antigenically, closer ancestral BA.2 other recently Omicron subvariants Altogether, these results highlight immune properties as well biology new underscore importance continuous surveillance informed decision-making development effective vaccines.

Language: Английский

Citations

30
Omicron-specific ultra-potent SARS-CoV-2 neutralizing antibodies targeting the N1/N2 loop of Spike N-terminal domain DOI Creative Commons
Xiaofeng Niu, Zhiqiang Li, Jing Wang

et al.

Emerging Microbes & Infections, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 3, 2024

A multitude of functional mutations continue to emerge on the N-terminal domain (NTD) spike protein in SARS-CoV-2 Omicron subvariants. Understanding immunogenicity NTD and properties antibodies elicited by it is crucial for comprehending impact viral fitness guiding vaccine design. In this study, we find that most NTD-targeting isolated from individuals with BA.5/BF.7 breakthrough infection (BTI) are ancestral (wildtype or WT)-reactive non-neutralizing. Surprisingly, identified five ultra-potent neutralizing (NAbs) can only bind but not WT NTD. Structural analysis revealed they a unique epitope N1/N2 loop interact receptor-binding (RBD) via light chain. These Omicron-specific NAbs achieve neutralization through ACE2 competition blockage ACE2-mediated S1 shedding. However, BA.2.86 BA.2.87.1, which carry insertions deletions loop, evade these antibodies. Together, provided detailed map antibody repertoire post-Omicron era, demonstrating their vulnerability enabled its evolutionary flexibility, despite potent neutralization. results function indels BA.2.86/JN.1 sublineage evading highlighted importance considering

Language: Английский

Citations

3
Distinct Patterns of SARS-CoV-2 BA.2.87.1 and JN.1 Variants in Immune Evasion, Antigenicity and Cell-Cell Fusion DOI Creative Commons

Pei Li,

Yajie Liu, Julia N. Faraone

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: March 11, 2024

The rapid evolution of SARS-CoV-2 variants presents a constant challenge to the global vaccination effort. In this study, we conducted comprehensive investigation into two newly emerged variants, BA.2.87.1 and JN.1, focusing on their neutralization resistance, infectivity, antigenicity, cell-cell fusion, spike processing. Neutralizing antibody (nAb) titers were assessed in diverse cohorts, including individuals who received bivalent mRNA vaccine booster, patients infected during BA.2.86/JN.1-wave, hamsters vaccinated with XBB.1.5-monovalent vaccine. We found that shows much less nAb escape from WT-BA.4/5 JN.1-wave breakthrough infection sera compared JN.1 XBB.1.5. Interestingly. is more resistant by XBB.15-monovalent-vaccinated hamster than BA.2.86/JN.1 XBB.1.5, but efficiently neutralized class III monoclonal S309, which largely fails neutralize BA.2.86/JN.1. Importantly, exhibits higher levels fusion activity, furin cleavage efficiency Antigenically, closer ancestral BA.2 other recently Omicron subvariants Altogether, these results highlight immune properties as well biology new underscore importance continuous surveillance informed decision-making development effective vaccines.

Language: Английский

Citations

2
SARS-CoV-2 Omicron BA.2.87.1 Exhibits Higher Susceptibility to Serum Neutralization Than EG.5.1 and JN.1 DOI Open Access
Qian Wang, Yicheng Guo,

Logan T. Schwanz

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: March 11, 2024

Abstract As SARS-CoV-2 continues to spread and mutate, tracking the viral evolutionary trajectory understanding functional consequences of its mutations remain crucial. Here, we characterized antibody evasion, ACE2 receptor engagement, infectivity highly mutated Omicron subvariant BA.2.87.1. Compared with other subvariants, including EG.5.1 current predominant JN.1, BA.2.87.1 exhibits less immune reduced comparable in Calu-3 lung cells. Intriguingly, two large deletions (Δ15-26 Δ136-146) N-terminal domain (NTD) spike protein facilitate subtly increased evasion but significantly diminish infectivity. Collectively, our data support announcement by USA CDC that public health risk posed appears be low.

Language: Английский

Citations

1
Omicron-specific ultra-potent SARS-CoV-2 neutralizing antibodies targeting the N1/N2 loop of Spike N-terminal domain DOI
Xiaofeng Niu, Zhiqiang Li, Jing Wang

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: July 10, 2024

Abstract A multitude of functional mutations continue to emerge on the N-terminal domain (NTD) spike protein in SARS-CoV-2 Omicron subvariants. Understanding immunogenicity NTD and properties antibodies elicited by it is crucial for comprehending impact viral fitness guiding vaccine design. In this study, we find that most NTD-targeting isolated from individuals with BA.5/BF.7 breakthrough infection (BTI) are ancestral (wildtype or WT)-reactive non-neutralizing. Surprisingly, identified five ultra-potent neutralizing (NAbs) can only bind but not WT NTD. Structural analysis revealed they a unique epitope N1/N2 loop interact receptor-binding (RBD) via light chain. These Omicron-specific NAbs achieve neutralization through ACE2 competition blockage ACE2-mediated S1 shedding. However, BA.2.86 BA.2.87.1, which carry insertions deletions loop, evade these antibodies. Together, provided detailed map antibody repertoire post-Omicron era, demonstrating their vulnerability enabled its evolutionary flexibility, despite potent neutralization. results highlighted importance considering Author Summary COVID-19 pandemic caused severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues be major global public health concern four years after emergence. The critical component glycoprotein, pivotal cellular entry serves as primary target therapeutics development. Characterizing sublineages understanding evolution Here, show vaccination induces majorly non-neutralizing Still, class specifically sublineages. neutralize virus competing blocking analyses reveal NTD, intriguingly glycoprotein. This special binding pattern, escaped BA.2.87.1 sublineages, shedding role recently emerged Our findings provide fresh insights into highlighting capacity evasion due flexibility. underscores carefully

Language: Английский

Citations

0