SARS-CoV-2 variant biology: immune escape, transmission and fitness

Nature Reviews Microbiology, Journal Year: 2023, Volume and Issue: unknown

Published: Jan. 18, 2023

In late 2020, after circulating for almost a year in the human population, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) exhibited major step change its adaptation to humans. These highly mutated forms of SARS-CoV-2 had enhanced rates transmission relative previous variants and were termed 'variants concern' (VOCs). Designated Alpha, Beta, Gamma, Delta Omicron, VOCs emerged independently from one another, turn each rapidly became dominant, regionally or globally, outcompeting variants. The success VOC previously dominant variant was enabled by altered intrinsic functional properties virus and, various degrees, changes antigenicity conferring ability evade primed immune response. increased fitness associated with is result complex interplay biology context changing immunity due both vaccination prior infection. this Review, we summarize literature on transmissibility variants, role mutations at furin spike cleavage site non-spike proteins, potential importance recombination success, evolution T cells, innate population immunity. shows complicated relationship among antigenicity, virulence, which has unpredictable implications future trajectory disease burden COVID-19.

Language: Английский

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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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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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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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Humoral immune evasion of the omicron subvariants BQ.1.1 and XBB

The Lancet Infectious Diseases, Journal Year: 2022, Volume and Issue: 23(1), P. 30 - 32

Published: Dec. 7, 2022

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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Deep mutational scans for ACE2 binding, RBD expression, and antibody escape in the SARS-CoV-2 Omicron BA.1 and BA.2 receptor-binding domains

PLoS Pathogens, Journal Year: 2022, Volume and Issue: 18(11), P. e1010951 - e1010951

Published: Nov. 18, 2022

SARS-CoV-2 continues to acquire mutations in the spike receptor-binding domain (RBD) that impact ACE2 receptor binding, folding stability, and antibody recognition. Deep mutational scanning prospectively characterizes impacts of on these biochemical properties, enabling rapid assessment new seen during viral surveillance. However, effects can change as virus evolves, requiring updated deep scans. We determined all single amino acid Omicron BA.1 BA.2 RBDs ACE2-binding affinity, RBD folding, escape from binding by LY-CoV1404 (bebtelovimab) monoclonal antibody. The some differ those measured ancestral Wuhan-Hu-1 background. These epistatic shifts largely resemble previously Alpha variant due convergent epistatically modifying N501Y substitution. variants show additional lineage-specific shifts, including examples phenomenon entrenchment causes Q498R substitutions present be more favorable background than earlier strains. In contrast, substitution Q493R exhibits no sign entrenchment, with derived state, R493, being unfavorable for Wuhan-Hu-1. Likely this reason, R493Q reversion has occurred sub-variants BA.4/BA.5 BA.2.75, where affinity buffer may potentiate concurrent antigenic change. Consistent prior studies, we find have reduced expression, identify candidate stabilizing ameliorate deficit. Last, our maps highlight a broadening sites compared datasets landscape inform ongoing efforts

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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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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