Fast evolution of SARS-CoV-2 BA.2.86 to JN.1 under heavy immune pressure

The Lancet Infectious Diseases, Год журнала: 2023, Номер 24(2), С. e70 - e72

Опубликована: Дек. 15, 2023

The SARS-CoV-2 saltation variant BA.2.86, which was quickly designated as a under monitoring after its emergence, has garnered global attention. Although BA.2.86 did not show substantial humoral immune escape and growth advantage compared with current dominant variants, such EG.5.1 HK.3, it showed remarkably high ACE2 binding affinity.1Yang S Yu Y Jian F et al.Antigenicity infectivity characterisation of BA.2.86.Lancet Infect Dis. 2023; 23: e457-e459Summary Full Text PDF PubMed Scopus (36) Google Scholar, 2Wannigama DL Amarasiri M Phattharapornjaroen P al.Tracing the new in community through wastewater surveillance Bangkok, Thailand.Lancet e464-e466Summary (11) 3Wang Q Guo Liu L receptor affinity spike.Nature. (published online Oct 23.)https://doi.org/10.1038/s41586-023-06750-wGoogle 4Uriu K Ito J Kosugi al.Transmissibility, infectivity, evasion variant.Lancet e460-e461Summary (29) 5Sheward DJ Yang Westerberg al.Sensitivity to prevailing neutralising antibody responses.Lancet e462-e463Summary (22) Scholar This increased affinity, coupled distinct antigenicity, could enable accumulate immune-evasive mutations during low-level populational transmission, akin previous evolution from BA.2.75 CH.1.1 XBB.6Cao Song W Wang al.Characterization enhanced Omicron BA.2.75.Cell Host Microbe. 2022; 30: 1527-1539Summary (74) 7Cao al.Imprinted immunity induces convergent RBD domain evolution.Nature. 614: 521-529PubMed 8Yue C al.ACE2 transmissibility XBB.1.5.Lancet 278-280Summary (108) 9Wang Li Z al.Evolving sublineage SARS-CoV-2.iScience. 26108254 Summary (3) With just one additional mutation (L455S) predecessor JN.1 rapidly became predominant France (figure A; appendix 1 p 12), surpassing both so-called FLip (L455F+F456L) strains. A thorough investigation into capability JN.1, particularly given few mutations, is imperative.FigureJN.1 shows profound decreased affinityShow full caption(A) Sequence percentages prevalent variants since August, 2023, including BA.2·86 (the original subvariants, except JN.1), HV.1, FLip+A475V, HK.3. advantages relative HK.3 past two months these strains are denoted legend within parentheses. Data collected covSPECTRUM. (B) 50% titer (NT50) convalescent plasma against measured individuals who received three CoronaVac doses had breakthrough infection BA.5 or BF.7 followed by XBB reinfection (n=54). Labels for geometric mean titers (GMT) located above each group, fold changes statistical significances indicated GMT labels. Below dashed line labels specifying numbers negative samples related limit detection (NT50=20). Two-tailed Wilcoxon signed-rank tests paired were used. *p<0·05, **p<0·01, ***p<0·001, ****p<0·0001. (C) human (angiotensin-converting enzyme 2) affinities (XBB.1.5+L455F+F456L), HV.1 (XBB.1.5+L452R+F456L), EG.5 (XBB.1.5+F456L), JD.1.1 (XBB.1.5+L455F+F456L+A475V), (BA.2.86+L455S) determined surface plasmon resonance sensorgrams. KD values (nM) displayed bars, all replicates represented points. (D) Class Nabs resistance pseudovirus XBB.1.5, EG.5, JD.1.1, IC50 (n=8). when D614G other labelled. (μg per mL) approved candidate monoclonal drugs targeting spike assessed pseudovirus. IC50=50% inhibitory concentration; KD=equilibrium dissociation constant; NAbs=neutralising antibodies; nM=nanomolarView Large Image Figure ViewerDownload Hi-res image Download (PPT) (A) nM=nanomolar We first study using pseudovirus-based neutralisation assays recovering infection. These individuals, having inactivated vaccines, subsequently contracted (XBB subvariants S486P substitution) infections. Our included cohorts, 27 participants post-vaccination infections another patients reinfected (appendix 2). significantly B). finding evidenced 2·1-fold decrease among post-BA.5 1·1-fold NT50 B; 13). Additionally, JN.1's surpassed that competitive (EG.5+L452R) (FLip+A475V). also lower their parental acquiring L452R A475V respectively, explaining advantages. As L455 on interface between 14),10Nutalai R Zhou D Tuekprakhon al.Potent cross-reactive antibodies following vaccinees.Cell. 185 (31.e18): 2116Summary (76) L455S change JN.1. By resonance, we found notable reduction domain, indicating capabilities come at expense reduced C). carried (XBB.1.5+FLip+A475V) resulted enhancing (XBB.1.5+FLip). However, affect affinity. Considering predominantly epitope antibodies, earlier research, our further examined response eight XBB.1·5-neutralising class antibodies.7Cao Pseudovirus addition ability evade D). effectively compensated BA.2.86's susceptibility this group Similarly, FLip+A475V (JD.1.1) (HK.3), offering insights trend variants. In terms therapeutic SA55 retained efficacy E). Together, findings suggest greatly compensation weakness antibodies. summary, inheriting antigenic diversity acquisition L455S, achieved extensive across 1, 2, 3 antibodies,1Yang higher resistant like JD.1·1, binding. evolutionary pattern, similar transition XBB,2Wannigama highlights importance closely BA.2.75, despite unremarkable capabilities. Such survive transmit low levels difference would allow them target populations have potential highly cost publication been corrected. corrected version appeared thelancet.com/infection January 3, 2024 YC inventor provisional patent applications BD series includes BD55–5514 (SA55). founder Singlomics Biopharmaceuticals. All authors declare no competing interests. .pdf (3.2 MB) Help pdf files Supplementary .xls (.02 xls 2 Correction Lancet Dis published Dec 15. https://doi.org/10.1016/S1473-3099(23)00744-2Yang S, Y, Xu al. Fast heavy pressure. https://doi.org/10.1016/S1473-3099(23)00744-2—In Correspondence, author's name should printed Yunlong Cao. corresponding email address read [email protected]. corrections made Jan 2024. Full-Text

Язык: Английский

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Virological characteristics of the SARS-CoV-2 XBB variant derived from recombination of two Omicron subvariants

Nature Communications, Год журнала: 2023, Номер 14(1)

Опубликована: Май 16, 2023

In late 2022, SARS-CoV-2 Omicron subvariants have become highly diversified, and XBB is spreading rapidly around the world. Our phylogenetic analyses suggested that emerged through recombination of two cocirculating BA.2 lineages, BJ.1 BM.1.1.1 (a progeny BA.2.75), during summer 2022. XBB.1 variant most profoundly resistant to BA.2/5 breakthrough infection sera date more fusogenic than BA.2.75. The breakpoint located in receptor-binding domain spike, each region recombinant spike confers immune evasion increases fusogenicity. We further provide structural basis for interaction between human ACE2. Finally, intrinsic pathogenicity male hamsters comparable or even lower multiscale investigation provides evidence suggesting first observed increase its fitness rather substitutions.

Язык: Английский

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Antigenicity and receptor affinity of SARS-CoV-2 BA.2.86 spike

Nature, Год журнала: 2023, Номер 624(7992), С. 639 - 644

Опубликована: Окт. 23, 2023

Язык: Английский

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Enhanced evasion of neutralizing antibody response by Omicron XBB.1.5, CH.1.1, and CA.3.1 variants

Cell Reports, Год журнала: 2023, Номер 42(5), С. 112443 - 112443

Опубликована: Апрель 18, 2023

Omicron subvariants continuingly challenge current vaccination strategies. Here, we demonstrate nearly complete escape of the XBB.1.5, CH.1.1, and CA.3.1 variants from neutralizing antibodies stimulated by three doses mRNA vaccine or BA.4/5 wave infection, but neutralization is rescued a BA.5-containing bivalent booster. CH.1.1 show strong immune monoclonal antibody S309. Additionally, spike proteins exhibit increased fusogenicity enhanced processing compared with BA.2. Homology modeling reveals key roles G252V F486P in resistance also enhancing receptor binding. Further, K444T/M L452R likely drive class II antibodies, whereas R346T G339H mutations could confer these two to S309-like antibodies. Overall, our results support need for administration continued surveillance subvariants.

Язык: Английский

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Repeated Omicron exposures override ancestral SARS-CoV-2 immune imprinting

Nature, Год журнала: 2023, Номер 625(7993), С. 148 - 156

Опубликована: Ноя. 22, 2023

Abstract The continuing emergence of SARS-CoV-2 variants highlights the need to update COVID-19 vaccine compositions. However, immune imprinting induced by vaccination based on ancestral (hereafter referred as WT) strain would compromise antibody response Omicron-based boosters 1–5 . Vaccination strategies counter are critically needed. Here we investigated degree and dynamics in mouse models human cohorts, especially focusing role repeated Omicron stimulation. In mice, efficacy single boosting is heavily limited when using that antigenically distinct from WT—such XBB variant—and this concerning situation could be mitigated a second booster. Similarly, humans, infections alleviate WT vaccination-induced generate broad neutralization responses both plasma nasal mucosa. Notably, deep mutational scanning-based epitope characterization 781 receptor-binding domain (RBD)-targeting monoclonal antibodies isolated infection revealed double exposure induce large proportion matured Omicron-specific have RBD epitopes WT-induced antibodies. Consequently, was largely mitigated, bias towards non-neutralizing observed exposures restored. On basis scanning profiles, identified evolution hotspots XBB.1.5 demonstrated these mutations further boost immune-evasion capability while maintaining high ACE2-binding affinity. Our findings suggest component should abandoned updating vaccines, individuals without prior receive two updated boosters.

Язык: Английский

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Antigenicity and infectivity characterisation of SARS-CoV-2 BA.2.86

The Lancet Infectious Diseases, Год журнала: 2023, Номер 23(11), С. e457 - e459

Опубликована: Сен. 19, 2023

Язык: Английский

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

Nature Communications, Год журнала: 2024, Номер 15(1)

Опубликована: Март 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.

Язык: Английский

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Enhanced transmissibility, infectivity, and immune resistance of the SARS-CoV-2 omicron XBB.1.5 variant

The Lancet Infectious Diseases, Год журнала: 2023, Номер 23(3), С. 280 - 281

Опубликована: Фев. 1, 2023

Язык: Английский

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Neutralization, effector function and immune imprinting of Omicron variants

Nature, Год журнала: 2023, Номер 621(7979), С. 592 - 601

Опубликована: Авг. 30, 2023

Abstract Currently circulating SARS-CoV-2 variants have acquired convergent mutations at hot spots in the receptor-binding domain 1 (RBD) of spike protein. The effects these on viral infection and transmission efficacy vaccines therapies remains poorly understood. Here we demonstrate that recently emerged BQ.1.1 XBB.1.5 bind host ACE2 with high affinity promote membrane fusion more efficiently than earlier Omicron variants. Structures BQ.1.1, XBB.1 BN.1 RBDs bound to fragment antigen-binding region S309 antibody (the parent for sotrovimab) human explain preservation binding through conformational selection, altered recognition immune evasion. We show sotrovimab binds avidly all variants, promotes Fc-dependent effector functions protects mice challenged hamsters XBB.1.5. Vaccine-elicited plasma antibodies cross-react trigger against current despite a reduced neutralizing activity, suggesting mechanism protection disease, exemplified by S309. Cross-reactive RBD-directed memory B cells remained dominant even after two exposures spikes, underscoring role persistent imprinting.

Язык: Английский

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The rapid rise of SARS‐CoV‐2 Omicron subvariants with immune evasion properties: XBB.1.5 and BQ.1.1 subvariants

MedComm, Год журнала: 2023, Номер 4(2)

Опубликована: Март 15, 2023

As the fifth variant of concern SARS-CoV-2 virus, Omicron (B.1.1.529) has quickly become dominant type among previous circulating variants worldwide. During wave, several subvariants have emerged, with some exhibiting greater infectivity and immune evasion, accounting for their fast spread across many countries. Recently, two subvariants, BQ.1 XBB lineages, including BQ.1.1, XBB.1, XBB.1.5, a global public health issue given ability to escape from therapeutic monoclonal antibodies herd immunity induced by prior coronavirus disease 2019 (COVID-19) vaccines, boosters, infection. In this respect, which been established harbor rare mutation F486P, demonstrates superior transmissibility compared other emerged as strain in This review provides comprehensive overview epidemiological features, spike mutations, evasion lineages. We expounded on mechanisms underlying mutations neutralizing vaccinated or convalescent COVID-19 individuals (mAbs) proposed strategies prevention against sublineages.

Язык: Английский

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