Distinct evolution of SARS-CoV-2 Omicron XBB and BA.2.86/JN.1 lineages combining increased fitness and antibody evasion

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: March 13, 2024

Abstract The unceasing circulation of SARS-CoV-2 leads to the continuous emergence novel viral sublineages. Here, we isolate and characterize XBB.1, XBB.1.5, XBB.1.9.1, XBB.1.16.1, EG.5.1.1, EG.5.1.3, XBF, BA.2.86.1 JN.1 variants, representing >80% circulating variants in January 2024. XBB subvariants carry few but recurrent mutations spike, whereas harbor >30 additional changes. These replicate IGROV-1 no longer Vero E6 are not markedly fusogenic. They potently infect nasal epithelial cells, with EG.5.1.3 exhibiting highest fitness. Antivirals remain active. Neutralizing antibody (NAb) responses from vaccinees BA.1/BA.2-infected individuals lower compared BA.1, without major differences between variants. An breakthrough infection enhances NAb against both BA.2.86 displays affinity ACE2 higher immune evasion properties BA.2.86.1. Thus, while distinct, evolutionary trajectory these combines increased fitness evasion.

Language: Английский

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Immune evasion, infectivity, and fusogenicity of SARS-CoV-2 BA.2.86 and FLip variants

Cell, Journal Year: 2024, Volume and Issue: 187(3), P. 585 - 595.e6

Published: Jan. 8, 2024

Evolution of SARS-CoV-2 requires the reassessment current vaccine measures. Here, we characterized BA.2.86 and XBB-derived variant FLip by investigating their neutralization alongside D614G, BA.1, BA.2, BA.4/5, XBB.1.5, EG.5.1 sera from 3-dose-vaccinated bivalent-vaccinated healthcare workers, XBB.1.5-wave-infected first responders, monoclonal antibody (mAb) S309. We assessed biology spikes measuring viral infectivity membrane fusogenicity. is less immune evasive compared to other XBB variants, consistent with antigenic distances. Importantly, distinct mAb S309 was unable neutralize BA.2.86, likely due a D339H mutation based on modeling. had relatively high fusogenicity in CaLu-3 cells but low fusion 293T-ACE2 some suggesting potentially different conformational stability spike. Overall, our study underscores importance surveillance need for updated COVID-19 vaccines.

Language: Английский

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Convergent evolution of SARS-CoV-2 XBB lineages on receptor-binding domain 455–456 synergistically enhances antibody evasion and ACE2 binding

PLoS Pathogens, Journal Year: 2023, Volume and Issue: 19(12), P. e1011868 - e1011868

Published: Dec. 20, 2023

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) XBB lineages have achieved dominance worldwide and keep on evolving. Convergent evolution of the receptor-binding domain (RBD) L455F F456L is observed, resulting in variants with substantial growth advantages, such as EG.5, FL.1.5.1, XBB.1.5.70, HK.3. Here, we show that neutralizing antibody (NAb) evasion drives convergent F456L, while epistatic shift caused by enables subsequent convergence through ACE2 binding enhancement further immune evasion. evade RBD-targeting Class 1 public NAbs, reducing neutralization efficacy breakthrough infection (BTI) reinfection convalescent plasma. Importantly, single substitution significantly dampens receptor binding; however, combination forms an adjacent residue flipping, which leads to enhanced NAbs resistance affinity. The perturbed mode exceptional NAb evasion, revealed structural analyses. Our results indicate flexibility contributed epistasis cannot be underestimated, potential SARS-CoV-2 RBD remains high.

Language: Английский

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Immune Evasion, Infectivity, and Fusogenicity of SARS-CoV-2 Omicron BA.2.86 and FLip Variants

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Sept. 12, 2023

Evolution of SARS-CoV-2 requires the reassessment current vaccine measures. Here, we characterized BA.2.86 and XBB-lineage variant FLip by investigating their neutralization alongside D614G, BA.1, BA.2, BA.4/5, XBB.1.5, EG.5.1 sera from 3-dose vaccinated bivalent healthcare workers, XBB.1.5-wave infected first responders, monoclonal antibody (mAb) S309. We assessed biology Spikes measuring viral infectivity membrane fusogenicity. is less immune evasive compared to other XBB variants, consistent with antigenic distances. Importantly, distinct mAb S309 was unable neutralize BA.2.86, likely due a D339H mutation based on modeling. had relatively high fusogenicity in CaLu-3 cells but low fusion 293T-ACE2 some suggesting potentially differences conformational stability Spike. Overall, our study underscores importance surveillance need for updated COVID-19 vaccines.

Language: Английский

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Neutralization escape, infectivity, and membrane fusion of JN.1-derived SARS-CoV-2 SLip, FLiRT, and KP.2 variants

Cell Reports, Journal Year: 2024, Volume and Issue: 43(8), P. 114520 - 114520

Published: July 17, 2024

Highlights•SLip, FLiRT, and KP.2 are poorly neutralized by bivalent-vaccinated sera•XBB.1.5-vaccinated hamster JN.1 patient sera SLip, KP.2•S mutations R346T, L455S, F456L alter ACE2 binding neutralization epitopes•SLip, spikes exhibit less fusion processing relative to JN.1SummaryWe investigate JN.1-derived subvariants for antibodies in vaccinated individuals, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected patients, or class III monoclonal antibody S309. Compared JN.1, KP.2, especially FLiRT increased resistance BA.2.86/JN.1-wave convalescent human sera. XBB.1.5 monovalent-vaccinated robustly neutralize but have reduced efficiency SLip. All resistant S309 show decreased infectivity, cell-cell fusion, spike JN.1. Modeling reveals that L455S SLip reduce ACE2, while R346T strengthens it. These three mutations, alongside D339H, key epitopes spike, likely explaining the sensitivity of these neutralization. Our findings highlight suggest future vaccine formulations should consider as an immunogen, although current monovalent could still offer adequate protection.Graphical abstract

Language: Английский

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

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

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Mutations in the SARS-CoV-2 spike receptor binding domain and their delicate balance between ACE2 affinity and antibody evasion

Protein & Cell, Journal Year: 2024, Volume and Issue: 15(6), P. 403 - 418

Published: March 4, 2024

Intensive selection pressure constrains the evolutionary trajectory of SARS-CoV-2 genomes and results in various novel variants with distinct mutation profiles. Point mutations, particularly those within receptor binding domain (RBD) spike (S) protein, lead to functional alteration both engagement monoclonal antibody (mAb) recognition. Here, we review data RBD point mutations possessed by major discuss their individual effects on ACE2 affinity immune evasion. Many single amino acid substitutions epitopes crucial for evasion capacity may conversely weaken affinity. However, this weakened effect could be largely compensated specific epistatic such as N501Y, thus maintaining overall protein all variants. The predominant direction evolution lies neither promoting nor evading mAb neutralization but a delicate balance between these two dimensions. Together, interprets how efficiently resist meanwhile is maintained, emphasizing significance comprehensive assessment mutations.

Language: Английский

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Characteristics of JN.1-derived SARS-CoV-2 subvariants SLip, FLiRT, and KP.2 in neutralization escape, infectivity and membrane fusion

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

Published: May 21, 2024

SARS-CoV-2 variants derived from the immune evasive JN.1 are on rise worldwide. Here, we investigated JN.1-derived subvariants SLip, FLiRT, and KP.2 for their ability to be neutralized by antibodies in bivalent-vaccinated human sera, XBB.1.5 monovalent-vaccinated hamster sera people infected during BA.2.86/JN.1 wave, class III monoclonal antibody (Mab) S309. We found that compared parental JN.1, SLip KP.2, especially exhibit increased resistance COVID-19 BA.2.86/JN.1-wave convalescent sera. Interestingly, monovalent vaccinated robustly FLiRT but had reduced efficiency SLip. These were resistant neutralization Mab In addition, aspects of spike protein biology including infectivity, cell-cell fusion processing, these subvariants, a decreased infectivity membrane relative correlating with processing. Homology modeling revealed L455S F456L mutations local hydrophobicity hence its binding ACE2. contrast, additional R346T mutation strengthened conformational support receptor-binding motif, thus counteracting effects F456L. three mutations, alongside D339H, which is present all sublineages, alter epitopes targeted therapeutic Mabs, I S309, explaining sensitivity Together, our findings provide insight into newly emerged suggest future vaccine formulations should consider as immunogen, although current could still offer adequate protection.

Language: Английский

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Anticipating the future of the COVID-19 pandemic: insights into the emergence of SARS-CoV-2 variant JN.1 and its projected impact on older adults

GeroScience, Journal Year: 2024, Volume and Issue: 46(3), P. 2879 - 2883

Published: Jan. 10, 2024

Language: Английский

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Recombinant XBB.1.5 boosters induce robust neutralization against KP.2- and KP.3-included JN.1 sublineages

Signal Transduction and Targeted Therapy, Journal Year: 2025, Volume and Issue: 10(1)

Published: Jan. 27, 2025

Abstract The newly emerged variants of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) demonstrate resistance to present therapeutic antibodies as well the capability evade vaccination-elicited antibodies. JN.1 sublineages were demonstrated one most immune-evasive variants, showing higher neutralization compared XBB.1.5. In this study, serum samples collected from adult participants including those who had gone through BA.5/BF.7, EG.5/HK.3 and XBB/JN.1 infection waves, characterized by different vaccination histories. We evaluated in these against pseudoviruses Omicron lineages. further investigated humoral immune response recombinant XBB vaccines estimated sublineages, KP.2 KP.3. Our results showed that sera previous circulating subvariant breakthrough infections exhibited low GMTs 50% all tested significantly elevated individuals received WSK-V102C or WSK-V102D boosters. Importantly, 4 months after a booster XBB.1.5, JN.1, JN.1.13, KP.3 3479, 1684, 1397, 1247 1298, with 9.86-, 9.79-, 8.73-, 8.66- 8.16-fold increase without booster, respectively, indicating boosting XBB.1.5 subunit still induced strong antibody responses sublineages. However, KP.3, revealed more than 2-fold decreases neutralizing titers suggesting enhanced evasion necessity boosters based on

Language: Английский

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