ACE2 binding and antibody evasion in enhanced transmissibility of XBB.1.5

The Lancet Infectious Diseases, Journal Year: 2023, Volume and Issue: 23(3), P. 278 - 280

Published: Feb. 3, 2023

Language: Английский

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Resistance of Omicron subvariants BA.2.75.2, BA.4.6, and BQ.1.1 to neutralizing antibodies

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: Feb. 14, 2023

Abstract Convergent evolution of SARS-CoV-2 Omicron BA.2, BA.4, and BA.5 lineages has led to the emergence several new subvariants, including BA.2.75.2, BA.4.6. BQ.1.1. The subvariant BQ.1.1 became predominant in many countries December 2022. subvariants carry an additional often redundant set mutations spike, likely responsible for increased transmissibility immune evasion. Here, we established a viral amplification procedure easily isolate strains. We examined their sensitivity 6 therapeutic monoclonal antibodies (mAbs) 72 sera from Pfizer BNT162b2-vaccinated individuals, with or without BA.1/BA.2 breakthrough infection. Ronapreve (Casirivimab Imdevimab) Evusheld (Cilgavimab Tixagevimab) lose antiviral efficacy against BA.2.75.2 BQ.1.1, whereas Xevudy (Sotrovimab) remaine weakly active. is also resistant Bebtelovimab. Neutralizing titers triply vaccinated individuals are low undetectable 4 months after boosting. A infection increases these titers, which remains about 18-fold lower than BA.1. Reciprocally, more efficiently neutralization BA.2.75.2. Thus, trajectory novel facilitates spread immunized populations raises concerns most available mAbs.

Language: 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, Journal Year: 2023, Volume and Issue: 42(5), P. 112443 - 112443

Published: April 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.

Language: Английский

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

Nature, Journal Year: 2023, Volume and Issue: 625(7993), P. 148 - 156

Published: Nov. 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.

Language: Английский

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Molecular fate-mapping of serum antibody responses to repeat immunization

Nature, Journal Year: 2023, Volume and Issue: 615(7952), P. 482 - 489

Published: Jan. 16, 2023

Language: 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, Journal Year: 2023, Volume and Issue: 4(2)

Published: March 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.

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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Update on the effectiveness of COVID-19 vaccines on different variants of SARS-CoV-2

International Immunopharmacology, Journal Year: 2023, Volume and Issue: 117, P. 109968 - 109968

Published: March 2, 2023

Language: Английский

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Enhanced transmissibility of XBB.1.5 is contributed by both strong ACE2 binding and antibody evasion

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

Published: Jan. 3, 2023

Abstract SARS-CoV-2 recombinant subvariant XBB.1.5 is growing rapidly in the United States, carrying an additional Ser486Pro substitution compared to XBB.1 and outcompeting BQ.1.1 other XBB sublineages. The underlying mechanism for such high transmissibility remains unclear. Here we show that exhibits a substantially higher hACE2-binding affinity XBB/XBB.1. Convalescent plasma samples from BA.1, BA.5, BF.7 breakthrough infection are significantly evaded by both XBB.1.5, with displaying slightly weaker immune evasion capability than XBB.1. Evusheld Bebtelovimab could not neutralize XBB.1/XBB.1.5, while Sotrovimab weakly reactive notably, SA55 still highly effective. fact showed comparable antibody but distinct suggests enhanced receptor-binding would indeed lead growth advantages. strong hACE2 binding of also enable its tolerance further escape mutations, which should be closely monitored.

Language: Английский

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Predicting the efficacy of variant-modified COVID-19 vaccine boosters

Nature Medicine, Journal Year: 2023, Volume and Issue: 29(3), P. 574 - 578

Published: March 1, 2023

Language: Английский

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