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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The evolution of SARS-CoV-2

Nature Reviews Microbiology, Journal Year: 2023, Volume and Issue: 21(6), P. 361 - 379

Published: April 5, 2023

Language: Английский

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SARS-CoV-2 variant evasion of monoclonal antibodies based on in vitro studies

Nature Reviews Microbiology, Journal Year: 2022, Volume and Issue: 21(2), P. 112 - 124

Published: Oct. 28, 2022

Language: Английский

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Virological characteristics of the SARS-CoV-2 Omicron BA.2 subvariants, including BA.4 and BA.5

Cell, Journal Year: 2022, Volume and Issue: 185(21), P. 3992 - 4007.e16

Published: Sept. 14, 2022

After the global spread of SARS-CoV-2 Omicron BA.2, some BA.2 subvariants, including BA.2.9.1, BA.2.11, BA.2.12.1, BA.4, and BA.5, emerged in multiple countries. Our statistical analysis showed that effective reproduction numbers these subvariants are greater than original BA.2. Neutralization experiments revealed immunity induced by BA.1/2 infections is less against BA.4/5. Cell culture BA.2.12.1 BA.4/5 replicate more efficiently human alveolar epithelial cells particularly, fusogenic We further provided structure spike receptor-binding domain binds to ACE2 considered how substitutions play roles binding immune evasion. Moreover, using hamsters suggested pathogenic multiscale investigations suggest risk particularly BA.4/5, health

Language: Английский

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A Detailed Overview of SARS-CoV-2 Omicron: Its Sub-Variants, Mutations and Pathophysiology, Clinical Characteristics, Immunological Landscape, Immune Escape, and Therapies

Viruses, Journal Year: 2023, Volume and Issue: 15(1), P. 167 - 167

Published: Jan. 5, 2023

The COVID-19 pandemic has created significant concern for everyone. Recent data from many worldwide reports suggest that most infections are caused by the Omicron variant and its sub-lineages, dominating all previously emerged variants. numerous mutations in Omicron’s viral genome sub-lineages attribute it a larger amount of fitness, owing to alteration transmission pathophysiology virus. With rapid change structure, sub-variants, namely BA.1, BA.2, BA.3, BA.4, BA.5, dominate community with an ability escape neutralization efficiency induced prior vaccination or infections. Similarly, several recombinant sub-variants Omicron, XBB, XBD, XBF, etc., have emerged, which better understanding. This review mainly entails changes due having higher number mutations. binding affinity, cellular entry, disease severity, infection rates, importantly, immune evading potential them discussed this review. A comparative analysis Delta other variants evolved before gives readers in-depth understanding landscape infection. Furthermore, discusses range abilities possessed approved antiviral therapeutic molecules neutralizing antibodies functional against sub-variants. evolution is causing infections, but broader aspect their not been explored. Thus, scientific should adopt elucidative approach obtain clear idea about recently including variants, so effective vaccines drugs can be achieved. This, turn, will lead drop cases and, finally, end pandemic.

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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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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Omicron BA.4/BA.5 escape neutralizing immunity elicited by BA.1 infection

Nature Communications, Journal Year: 2022, Volume and Issue: 13(1)

Published: Aug. 10, 2022

SARS-CoV-2 Omicron (B.1.1.529) BA.4 and BA.5 sub-lineages, first detected in South Africa, have changes relative to BA.1 including substitutions the spike receptor binding domain. Here we isolated live viruses measured BA.4/BA.5 neutralization elicited by infection either absence or presence of previous vaccination as well from without infection. In BA.1-infected unvaccinated individuals, declines 7.6-fold for 7.5-fold BA.5. vaccinated individuals with subsequent infection, decreases 3.2-fold 2.6-fold The fold-drop versus ancestral virus this group is 4.0-fold BA.1, 12.9-fold BA.4, 10.3-fold contrast, escape similar immunity: 19.8-fold 19.6-fold 20.9-fold These results show considerable immunity which moderated may indicate that strongest selective advantage evading unvaccinated, infected individuals.

Language: Английский

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SARS-CoV-2 Omicron BA.5: Evolving tropism and evasion of potent humoral responses and resistance to clinical immunotherapeutics relative to viral variants of concern

EBioMedicine, Journal Year: 2022, Volume and Issue: 84, P. 104270 - 104270

Published: Sept. 18, 2022

BackgroundGenetically distinct viral variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been recorded since January 2020. The introduction global vaccine programs has contributed to lower COVID-19 hospitalisation and mortality rates, particularly in developed countries. In late 2021, Omicron BA.1 emerged, with substantially altered genetic differences clinical effects from other concern. Shortly after dominating spread early 2022, was supplanted by the genetically lineage BA.2. A sub-lineage BA.2, designated BA.5, presently an outgrowth advantage over BA.2 sub-lineages. Here we study neutralisation BA.1, BA.5 pre-Omicron using a range convalescent sera therapeutic monoclonal antibodies live virus assay. Using primary nasopharyngeal swabs, also tested relative fitness compared lineages their ability use ACE2-TMPRSS2 pathway.MethodsUsing low passage isolates Clade A.2.2, Beta, Delta, determined humoral vitro vaccinated cohorts, concentrated human IgG pooled thousands plasma donors, licensed antibody therapies. We then infectivity particle ratios samples expanded engineered ACE2/TMPRSS2 cell line presence absence TMPRSS2 inhibitor Nafamostat.FindingsPeak responses 3 doses BNT162b2 were associated 9-fold reduction for BA.5. Concentrated donors vaccination breakthrough infections greater breadth neutralisation, although potency still reduced 7-fold across all lineages. Testing grade revealed 14.3-fold Evusheld 16.8-fold Sotrovimab Whilst attenuated entry, observed be equivalent that 2020 circulating clade had sensitivity Nafamostat.InterpretationObservations support significantly escape neutralising and/or responses. Potency is differs key difference sub-variants reversion tropism back well-known pathway, utilised efficiently Monitoring if these changes influence transmission disease severity will ongoing tracking management waves globally.FundingThis work primarily supported Australian Medical Foundation research grants MRF2005760 (ST, GM & WDR), MRF2001684 (ADK ST) Research Future Fund Antiviral Development Call grant (WDR), (MRFF2001684, ADK SGT) New South Wales Health Grants Round (SGT).

Language: Английский

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