Alarming antibody evasion properties of rising SARS-CoV-2 BQ and XBB subvariants

Cell, Journal Year: 2022, Volume and Issue: 186(2), P. 279 - 286.e8

Published: Dec. 14, 2022

The BQ and XBB subvariants of SARS-CoV-2 Omicron are now rapidly expanding, possibly due to altered antibody evasion properties deriving from their additional spike mutations. Here, we report that neutralization BQ.1, BQ.1.1, XBB, XBB.1 by sera vaccinees infected persons was markedly impaired, including individuals boosted with a WA1/BA.5 bivalent mRNA vaccine. Titers against were lower 13- 81-fold 66- 155-fold, respectively, far beyond what had been observed date. Monoclonal antibodies capable neutralizing the original variant largely inactive these new subvariants, responsible individual mutations identified. These found have similar ACE2-binding affinities as predecessors. Together, our findings indicate present serious threats current COVID-19 vaccines, render all authorized antibodies, may gained dominance in population because advantage evading antibodies.

Language: Английский

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Imprinted SARS-CoV-2 humoral immunity induces convergent Omicron RBD evolution

Nature, Journal Year: 2022, Volume and Issue: unknown

Published: Dec. 19, 2022

Abstract Continuous evolution of Omicron has led to a rapid and simultaneous emergence numerous variants that display growth advantages over BA.5 (ref. 1 ). Despite their divergent evolutionary courses, mutations on receptor-binding domain (RBD) converge several hotspots. The driving force destination such sudden convergent its effect humoral immunity remain unclear. Here we demonstrate these can cause evasion neutralizing antibody drugs convalescent plasma, including those from breakthrough infection, while maintaining sufficient ACE2-binding capability. BQ.1.1.10 (BQ.1.1 + Y144del), BA.4.6.3, XBB CH.1.1 are the most antibody-evasive strains tested. To delineate origin evolution, determined escape mutation profiles neutralization activity monoclonal antibodies isolated individuals who had BA.2 infections 2,3 . Owing immune imprinting, especially infection reduced diversity binding sites increased proportions non-neutralizing clones, which, in turn, focused pressure promoted RBD. Moreover, show RBD could be accurately inferred by deep mutational scanning 4,5 , trends BA.2.75 subvariants well foreseen through constructed pseudovirus mutants. These results suggest current herd vaccine boosters may not efficiently prevent variants.

Language: Английский

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

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

Published: May 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.

Language: Английский

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Enhanced neutralization resistance of SARS-CoV-2 Omicron subvariants BQ.1, BQ.1.1, BA.4.6, BF.7, and BA.2.75.2

Cell Host & Microbe, Journal Year: 2022, Volume and Issue: 31(1), P. 9 - 17.e3

Published: Nov. 22, 2022

Language: Английский

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Imprinted SARS-CoV-2 humoral immunity induces convergent Omicron RBD evolution

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2022, Volume and Issue: unknown

Published: Sept. 16, 2022

Abstract Continuous evolution of Omicron has led to a rapid and simultaneous emergence numerous variants that display growth advantages over BA. 5. Despite their divergent evolutionary courses, mutations on receptor-binding domain (RBD) converge several hotspots. The driving force destination such convergent its impact humoral immunity remain unclear. Here, we demonstrate these can cause striking evasion neutralizing antibody (NAb) drugs convalescent plasma, including those from BA.5 breakthrough infection, while maintaining sufficient ACE2 binding capability. BQ.1.1.10, BA.4.6.3, XBB, CH. 1.1 are the most antibody-evasive strain tested, even exceeding SARS-CoV-1 level. To delineate origin evolution, determined escape mutation profiles neutralization activity monoclonal antibodies (mAbs) isolated BA.2 breakthrough-infection convalescents. Importantly, due immune imprinting, especially infection caused significant reductions in epitope diversity NAbs increased proportion non-neutralizing mAbs, which turn concentrated pressure promoted evolution. Moreover, showed RBD could be accurately inferred by integrated deep mutational scanning (DMS) profiles, trends BA.2.75/BA.5 subvariants well-simulated through constructed pseudovirus mutants. Together, our results suggest current herd vaccine boosters may not provide good protection against infection. Broad-spectrum SARS-CoV-2 vaccines NAb development should highly prioritized, mutants help examine effectiveness advance.

Language: Английский

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Characterization of the enhanced infectivity and antibody evasion of Omicron BA.2.75

Cell Host & Microbe, Journal Year: 2022, Volume and Issue: 30(11), P. 1527 - 1539.e5

Published: Oct. 4, 2022

Recently emerged SARS-CoV-2 Omicron subvariant, BA.2.75, displayed a growth advantage over circulating BA.2.38, BA.2.76, and BA.5 in India. However, the underlying mechanisms for enhanced infectivity, especially compared with BA.5, remain unclear. Here, we show that BA.2.75 exhibits substantially higher affinity host receptor angiotensin-converting enzyme 2 (ACE2) than other variants. Structural analyses of spike shows its decreased thermostability increased frequency binding domain (RBD) "up" conformation under acidic conditions, suggesting low-pH-endosomal cell entry. Relative to BA.4/BA.5, reduced evasion humoral immunity from BA.1/BA.2 breakthrough-infection convalescent plasma but greater Delta plasma. also weaker neutralization against mainly due BA.2.75's distinct neutralizing antibody (NAb) escape pattern. Antibody therapeutics Evusheld Bebtelovimab effective BA.2.75. These results suggest may prevail after receptor-binding capability could support further immune-evasive mutations.

Language: Английский

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

Nature, Journal Year: 2023, Volume and Issue: 624(7992), P. 639 - 644

Published: Oct. 23, 2023

Language: Английский

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A pseudovirus system enables deep mutational scanning of the full SARS-CoV-2 spike

Cell, Journal Year: 2023, Volume and Issue: 186(6), P. 1263 - 1278.e20

Published: Feb. 13, 2023

A major challenge in understanding SARS-CoV-2 evolution is interpreting the antigenic and functional effects of emerging mutations viral spike protein. Here, we describe a deep mutational scanning platform based on non-replicative pseudotyped lentiviruses that directly quantifies how large numbers impact antibody neutralization pseudovirus infection. We apply this to produce libraries Omicron BA.1 Delta spikes. These each contain ∼7,000 distinct amino acid context up ∼135,000 unique mutation combinations. use these map escape from neutralizing antibodies targeting receptor-binding domain, N-terminal S2 subunit spike. Overall, work establishes high-throughput safe approach measure ∼10

Language: Английский

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Convergent evolution of SARS-CoV-2 Omicron subvariants leading to the emergence of BQ.1.1 variant

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

Published: May 11, 2023

In late 2022, various Omicron subvariants emerged and cocirculated worldwide. These variants convergently acquired amino acid substitutions at critical residues in the spike protein, including R346, K444, L452, N460, F486. Here, we characterize convergent evolution of properties one recent lineage concern, BQ.1.1. Our phylogenetic analysis suggests that these five are recurrently acquired, particularly younger lineages. Epidemic dynamics modelling increase viral fitness, a large proportion fitness variation within lineages can be explained by substitutions. Compared to BA.5, BQ.1.1 evades breakthrough BA.2 BA.5 infection sera more efficiently, as demonstrated neutralization assays. The pathogenicity hamsters is lower than BA.5. multiscale investigations illuminate evolutionary rules governing for known 2022.

Language: Английский

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Bivalent Omicron BA.1–Adapted BNT162b2 Booster in Adults Older than 55 Years

New England Journal of Medicine, Journal Year: 2023, Volume and Issue: 388(3), P. 214 - 227

Published: Jan. 18, 2023

The emergence of immune-escape variants severe acute respiratory syndrome coronavirus 2 warrants the use sequence-adapted vaccines to provide protection against disease 2019.

Language: Английский

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