Humoral immune escape by current SARS-CoV-2 variants BA.2.86 and JN.1, December 2023

Eurosurveillance, Год журнала: 2024, Номер 29(2)

Опубликована: Янв. 11, 2024

Variant BA.2.86 and its descendant, JN.1, of SARS-CoV-2 are rising in incidence across Europe globally. We isolated recent BA.2.86, EG.5, XBB.1.5 earlier variants. tested live virus neutralisation sera taken September 2023 from vaccinated exposed healthy persons (n = 39). found clear escape against variants but no specific pronounced for or JN.1. Neutralisation corresponds to variant predominance may not be causative the upsurge JN.1 incidence.

Язык: Английский

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Spike deep mutational scanning helps predict success of SARS-CoV-2 clades

Nature, Год журнала: 2024, Номер 631(8021), С. 617 - 626

Опубликована: Июль 3, 2024

SARS-CoV-2 variants acquire mutations in the spike protein that promote immune evasion

Язык: Английский

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Post-pandemic memory T cell response to SARS-CoV-2 is durable, broadly targeted, and cross-reactive to the hypermutated BA.2.86 variant

Cell Host & Microbe, Год журнала: 2024, Номер 32(2), С. 162 - 169.e3

Опубликована: Янв. 10, 2024

Ongoing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) evolution has given rise to recombinant Omicron lineages that dominate globally (XBB.1), as well the emergence of hypermutated variants (BA.2.86). In this context, durable and cross-reactive T cell immune memory is critical for continued protection against COVID-19. We examined responses SARS-CoV-2 approximately 1.5 years since first emerged. describe sustained CD4+ CD8+ spike-specific in healthcare workers South Africa (n = 39) who were vaccinated experienced at least one infection. Spike-specific cells are highly with all tested, including BA.2.86. Abundant nucleocapsid membrane-specific detectable most participants. The bulk SARS-CoV-2-specific have an early-differentiated phenotype, explaining their persistent nature. Overall, hybrid immunity leads accumulation spike non-spike evident 3.5 after start pandemic, preserved recognition mutated variants.

Язык: Английский

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Differential protection against SARS-CoV-2 reinfection pre- and post-Omicron

Nature, Год журнала: 2025, Номер unknown

Опубликована: Фев. 5, 2025

Abstract The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has rapidly evolved over short timescales, leading to the emergence of more transmissible variants such as Alpha and Delta 1–3 . arrival Omicron variant marked a major shift, introducing numerous extra mutations in spike gene compared with earlier 1,2 These evolutionary changes have raised concerns regarding their potential impact on immune evasion, disease severity effectiveness vaccines treatments 1,3 In this epidemiological study, we identified two distinct patterns protective effect natural infection against reinfection versus pre-Omicron eras. Before Omicron, provided strong durable protection reinfection, minimal waning time. However, during era, was robust only for those recently infected, declining time diminishing within year. results demonstrate that SARS-CoV-2 is shaped by dynamic interaction between host immunity viral evolution, contrasting before after Omicron’s first wave. This shift suggests change pressures, intrinsic transmissibility driving adaptation escape becoming dominant post-Omicron, underscoring need periodic vaccine updates sustain immunity.

Язык: Английский

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Antigenic cartography using variant-specific hamster sera reveals substantial antigenic variation among Omicron subvariants

Proceedings of the National Academy of Sciences, Год журнала: 2024, Номер 121(32)

Опубликована: Июль 30, 2024

Severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) has developed substantial antigenic variability. As the majority of population now pre-existing immunity due to infection or vaccination, use experimentally generated animal immune sera can be valuable for measuring differences between virus variants. Here, we immunized Syrian hamsters by two successive infections with one nine SARS-CoV-2 Their were titrated against 16 variants, and resulting titers visualized using cartography. The map shows a condensed cluster containing all pre-Omicron variants (D614G, Alpha, Delta, Beta, Mu, an engineered B.1+E484K variant) considerably more diversity among selected panel Omicron subvariants (BA.1, BA.2, BA.4/BA.5, BA.5 descendants BF.7 BQ.1.18, BA.2.75 descendant BN.1.3.1, BA.2-derived recombinants XBB.2 EG.5.1, BA.2.86 JN.1). Some as antigenically distinct from each other wildtype is BA.1 variant. Compared measured in human sera, hamster are higher magnitude, show less fold change, result compact topology. results highlight potential continued characterization SARS-CoV-2.

Язык: Английский

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The mutation rate of SARS-CoV-2 is highly variable between sites and is influenced by sequence context, genomic region, and RNA structure

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2025, Номер unknown

Опубликована: Янв. 8, 2025

Abstract RNA viruses like SARS-CoV-2 have a high mutation rate, which contributes to their rapid evolution. The rate of mutations depends on the type (e.g., A → C , G etc.) and can vary between sites in viral genome. Understanding this variation shed light mutational processes at play, is crucial for quantitative modeling Using millions available full-genome sequences, we estimate rates synonymous all 12 possible nucleotide types examine how much these sites. We find surprisingly level variability several striking patterns: four suddenly increase one two gene boundaries; most strongly depend site’s local sequence context, with up 56-fold differences contexts; consistent previous study, some are lower engaged secondary structure. simple log-linear model features explains ∼15-60% fold-variation sites, depending type; more complex models only modestly improve predictive power out sample. fitness effect each based number times it actually occurs versus expected occur model. identify small regions genome where or noncoding less often than expected, indicative strong purifying selection that independent protein sequence. Overall, work expands our basic understanding SARS-CoV-2’s evolution by characterizing virus’s process individual uncovering patterns arise from unknown mechanisms.

Язык: Английский

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Full-spike deep mutational scanning helps predict the evolutionary success of SARS-CoV-2 clades

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2023, Номер unknown

Опубликована: Ноя. 14, 2023

SARS-CoV-2 variants acquire mutations in spike that promote immune evasion and impact other properties contribute to viral fitness such as ACE2 receptor binding cell entry. Knowledge of how affect these phenotypes can provide insight into the current potential future evolution virus. Here we use pseudovirus deep mutational scanning measure >9,000 across full XBB.1.5 BA.2 spikes binding, entry, or escape from human sera. We find outside receptor-binding domain (RBD) have meaningfully impacted during evolution. also neutralization by serum individuals who recently had infections. The strongest are RBD at sites 357, 420, 440, 456, 473-however, antigenic impacts vary individuals. identify strong RBD; however many them decrease suggesting they act modulating conformation. Notably, growth rates clades be explained substantial part measured effects on phenotypes, our data could enable better prediction

Язык: Английский

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Ensemble-Based Mutational Profiling and Network Analysis of the SARS-CoV-2 Spike Omicron XBB Lineages for Interactions with the ACE2 Receptor and Antibodies: Cooperation of Binding Hotspots in Mediating Epistatic Couplings Underlies Binding Mechanism and Immune Escape

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(8), С. 4281 - 4281

Опубликована: Апрель 12, 2024

In this study, we performed a computational study of binding mechanisms for the SARS-CoV-2 spike Omicron XBB lineages with host cell receptor ACE2 and panel diverse class one antibodies. The central objective investigation was to examine molecular factors underlying epistatic couplings among convergent evolution hotspots that enable optimal balancing antibody evasion variants BA.1, BA2, BA.3, BA.4/BA.5, BQ.1.1, XBB.1, XBB.1.5, XBB.1.5 + L455F/F456L. By combining evolutionary analysis, dynamics simulations, ensemble-based mutational scanning protein residues in complexes ACE2, identified structural stability affinity are consistent results biochemical studies. agreement deep experiments, our quantitative analysis correctly reproduced strong variant-specific effects BA.2 variants. It shown Y453W F456L mutations can enhance when coupled Q493 while these become destabilized R493 position variant. provided rationale mechanism variants, showing role Q493/R493 hotspot modulating between sites L455F lineages. receptors antibodies provide experimental evidence interactions physically proximal Y501, R498, Q493, L455F, determine binding, F486P instrumental mediating broad resistance. supports which impact on is mediated through small group universal hotspots, effect immune could be more variant-dependent modulated by conformationally adaptable regions.

Язык: Английский

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Emerging variants develop total escape from potent monoclonal antibodies induced by BA.4/5 infection

Nature Communications, Год журнала: 2024, Номер 15(1)

Опубликована: Апрель 16, 2024

Abstract The rapid evolution of SARS-CoV-2 is driven in part by a need to evade the antibody response face high levels immunity. Here, we isolate spike (S) binding monoclonal antibodies (mAbs) from vaccinees who suffered vaccine break-through infections with Omicron sub lineages BA.4 or BA.5. Twenty eight potent are isolated and characterised functionally, some cases structurally. Since emergence BA.4/5, has continued accrue mutations S protein, understand this characterize neutralization large panel variants demonstrate steady attrition BA.4/5 mAbs culminating total loss function recent XBB.1.5.70 containing so-called ‘FLip’ at positions 455 456. Interestingly, activity regained on recently reported variant BA.2.86.

Язык: Английский

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SARS-CoV-2 Omicron: Viral Evolution, Immune Evasion, and Alternative Durable Therapeutic Strategies

Viruses, Год журнала: 2024, Номер 16(5), С. 697 - 697

Опубликована: Апрель 28, 2024

Since the SARS-CoV-2 Omicron virus has gained dominance worldwide, its continual evolution with unpredictable mutations and patterns revoked all authorized immunotherapeutics. Rapid viral also necessitated several rounds of vaccine updates in order to provide adequate immune protection. It remains imperative understand how evolves into different subvariants causes escape as this could help reevaluate current intervention strategies mostly implemented clinics emergency measures counter pandemic and, importantly, develop new solutions. Here, we a review focusing on major events evolution, including features spike mutation that lead evasion against monoclonal antibody (mAb) therapy vaccination, suggest alternative durable options such ACE2-based experimental therapies superior mAbs address unprecedented virus. In addition, type unique virus-trapping molecules can zoonotic SARS coronaviruses, either from unknown animal hosts or established wild-life reservoirs SARS-CoV-2, even seasonal alpha coronavirus NL63 depends human ACE2 for infection.

Язык: Английский

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