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 Omicron is an immune escape variant with an altered cell entry pathway

Nature Microbiology, Journal Year: 2022, Volume and Issue: 7(8), P. 1161 - 1179

Published: July 7, 2022

Vaccines based on the spike protein of SARS-CoV-2 are a cornerstone public health response to COVID-19. The emergence hypermutated, increasingly transmissible variants concern (VOCs) threaten this strategy. Omicron (B.1.1.529), fifth VOC be described, harbours multiple amino acid mutations in spike, half which lie within receptor-binding domain. Here we demonstrate substantial evasion neutralization by BA.1 and BA.2 vitro using sera from individuals vaccinated with ChAdOx1, BNT162b2 mRNA-1273. These data were mirrored reduction real-world vaccine effectiveness that was partially restored booster vaccination. did not induce cell syncytia favoured TMPRSS2-independent endosomal entry pathway, these phenotypes mapping distinct regions protein. Impaired fusion determined domain, while mapped S2 Such marked changes antigenicity replicative biology may underlie rapid global spread altered pathogenicity variant.

Language: Английский

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Respiratory mucosal immunity against SARS-CoV-2 after mRNA vaccination

Science Immunology, Journal Year: 2022, Volume and Issue: 7(76)

Published: July 19, 2022

SARS-CoV-2 mRNA vaccination induces robust humoral and cellular immunity in the circulation; however, it is currently unknown whether elicits effective immune responses respiratory tract, particularly against variants of concern (VOCs), including Omicron. We compared S-specific total neutralizing antibody responses, B T cell immunity, bronchoalveolar lavage fluid (BAL) blood COVID-19-vaccinated individuals hospitalized patients. Vaccinated had significantly lower levels D614G, Delta (B.1.617.2), Omicron BA.1.1 BAL with COVID-19 convalescents despite blood. Furthermore, induced circulating but contrast to convalescents, these were absent vaccinated individuals. Using a mouse immunization model, we demonstrated that systemic alone weak mucosal especially mice; combination plus adenovirus-S strong not only ancestral virus also variant. Together, our study supports contention current vaccines are highly severe disease development, likely through recruiting during reinfection, offer limited protection breakthrough infection, by sublineage. Hence, booster needed establish sterilizing tract SARS-CoV-2, infection sublineage future VOCs.

Language: Английский

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The Impact of Evolving SARS-CoV-2 Mutations and Variants on COVID-19 Vaccines

mBio, Journal Year: 2022, Volume and Issue: 13(2)

Published: March 30, 2022

The emergence of several new variants severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in recent months has raised concerns around the potential impact on ongoing vaccination programs. Data from clinical trials and real-world evidence suggest that current vaccines remain highly effective against alpha variant (B.1.1.7), while some have reduced efficacy effectiveness symptomatic disease caused by beta (B.1.351) delta (B.1.617.2); however, hospitalization remains high. Although data primary regimen omicron (B.1.1.529) are limited, booster programs using mRNA been shown to restore protection infection (regardless vaccine used for regimen) maintain high hospitalization. However, wanes with time after dose. Studies demonstrated reductions varying magnitude neutralizing activity vaccine-elicited antibodies a range SARS-CoV-2 variants, particular exhibiting partial immune escape. suggests T-cell responses preserved across platforms, regardless concern. Nevertheless, various mitigation strategies under investigation address or future including modification certain (including omicron), multivalent formulations, different delivery mechanisms.

Language: Английский

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Innate immune evasion strategies of SARS-CoV-2

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

Published: Jan. 11, 2023

Language: Английский

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Daily longitudinal sampling of SARS-CoV-2 infection reveals substantial heterogeneity in infectiousness

Nature Microbiology, Journal Year: 2022, Volume and Issue: 7(5), P. 640 - 652

Published: April 28, 2022

Language: Английский

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The Evolution and Biology of SARS-CoV-2 Variants

Cold Spring Harbor Perspectives in Medicine, Journal Year: 2022, Volume and Issue: 12(5), P. a041390 - a041390

Published: April 20, 2022

Our understanding of the still unfolding severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic would have been extremely limited without study genetics and evolution this new human coronavirus. Large-scale genome-sequencing efforts provided close to real-time tracking global spread diversification SARS-CoV-2 since its entry into population in late 2019. These data underpinned analysis origins, epidemiology, adaptations population: principally immune evasion increasing transmissibility. SARS-CoV-2, despite being a pathogen, was highly capable human-to-human transmission. During rapid humans, has evolved independent forms, so-called "variants concern," that are better optimized for The most important adaptation bat progenitor both SARS-CoV-1 infection (and other mammals) is use angiotensin-converting enzyme (ACE2) receptor. Relaxed structural constraints provide plasticity SARS-related spike protein permitting it accommodate significant amino acid replacements antigenic consequence compromising ability bind ACE2. Although bulk research justifiably concentrated on viral as main determinant changes transmissibility, there accumulating evidence contribution regions proteome virus-host interaction. Whereas levels community transmission recombinants genetically distinct variants at present low, when divergent cocirculate, recombination between clades detected, risk viruses with properties emerge. Applying computational machine learning methods genome sequence sets generate experimentally verifiable predictions will serve an early warning system novel variant surveillance be future vaccine planning. Omicron, latest concern, focused attention step change events, "shift," opposed incremental "drift" antigenicity. Both increase transmissibility shift Omicron led readily causing infections fully vaccinated and/or previously infected. Omicron's virulence, while reduced relative concern replaced, Delta, very much premised past exposure individuals clear signal boosted vaccination protects from disease. Currently, proven itself dangerous pathogen unpredictable evolutionary capacity, leading too great not ensure all world screened by sequencing, protected through available affordable vaccines, non-punitive strategies place detecting responding concern.

Language: Английский

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The role of NSP6 in the biogenesis of the SARS-CoV-2 replication organelle

Nature, Journal Year: 2022, Volume and Issue: 606(7915), P. 761 - 768

Published: May 12, 2022

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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