Bivalent SARS-CoV-2 mRNA vaccines increase breadth of neutralization and protect against the BA.5 Omicron variant in mice

Nature Medicine, Год журнала: 2022, Номер 29(1), С. 247 - 257

Опубликована: Окт. 20, 2022

Язык: 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, Год журнала: 2023, Номер 42(5), С. 112443 - 112443

Опубликована: Апрель 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.

Язык: Английский

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

Cell, Год журнала: 2023, Номер 186(6), С. 1263 - 1278.e20

Опубликована: Фев. 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

Язык: 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, Год журнала: 2022, Номер 84, С. 104270 - 104270

Опубликована: Сен. 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).

Язык: Английский

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CRISPR-Cas13a-powered electrochemical biosensor for the detection of the L452R mutation in clinical samples of SARS-CoV-2 variants

Journal of Nanobiotechnology, Год журнала: 2023, Номер 21(1)

Опубликована: Апрель 29, 2023

Since the end of 2019, a highly contagious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has deprived numerous lives worldwide, called COVID-19. Up to date, omicron is latest variant concern, and BA.5 replacing BA.2 become main subtype rampaging worldwide. These subtypes harbor an L452R mutation, which increases their transmissibility among vaccinated people. Current methods for identifying SARS-CoV-2 variants are mainly based on polymerase chain reaction (PCR) followed gene sequencing, making time-consuming processes expensive instrumentation indispensable. In this study, we developed rapid ultrasensitive electrochemical biosensor achieve goals high sensitivity, ability distinguishing variants, direct detection RNAs from viruses simultaneously. We used electrodes made MXene-AuNP (gold nanoparticle) composites improved sensitivity CRISPR/Cas13a system specificity in detecting single-base mutation clinical samples. Our will be excellent supplement RT-qPCR method enabling early diagnosis quick distinguishment Omicron more potential that might arise future.

Язык: Английский

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