Distinct evolution of SARS-CoV-2 Omicron XBB and BA.2.86/JN.1 lineages combining increased fitness and antibody evasion

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

Опубликована: Март 13, 2024

Abstract The unceasing circulation of SARS-CoV-2 leads to the continuous emergence novel viral sublineages. Here, we isolate and characterize XBB.1, XBB.1.5, XBB.1.9.1, XBB.1.16.1, EG.5.1.1, EG.5.1.3, XBF, BA.2.86.1 JN.1 variants, representing >80% circulating variants in January 2024. XBB subvariants carry few but recurrent mutations spike, whereas harbor >30 additional changes. These replicate IGROV-1 no longer Vero E6 are not markedly fusogenic. They potently infect nasal epithelial cells, with EG.5.1.3 exhibiting highest fitness. Antivirals remain active. Neutralizing antibody (NAb) responses from vaccinees BA.1/BA.2-infected individuals lower compared BA.1, without major differences between variants. An breakthrough infection enhances NAb against both BA.2.86 displays affinity ACE2 higher immune evasion properties BA.2.86.1. Thus, while distinct, evolutionary trajectory these combines increased fitness evasion.

Язык: Английский

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Persistent immune imprinting occurs after vaccination with the COVID-19 XBB.1.5 mRNA booster in humans

Immunity, Год журнала: 2024, Номер 57(4), С. 904 - 911.e4

Опубликована: Март 14, 2024

Immune imprinting describes how the first exposure to a virus shapes immunological outcomes of subsequent exposures antigenically related strains. Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) Omicron breakthrough infections and bivalent COVID-19 vaccination primarily recall cross-reactive memory B cells induced by prior Wuhan-Hu-1 spike mRNA rather than priming Omicron-specific naive cells. These findings indicate that immune occurs after repeated exposures, but whether it can be overcome remains unclear. To understand persistence imprinting, we investigated plasma antibody responses administration updated XBB.1.5 vaccine booster. We showed booster elicited neutralizing against current variants were dominated pre-existing previously spike. Therefore, persists multiple spikes through infection, including post vaccination, which will need considered guide future vaccination.

Язык: Английский

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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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SARS-CoV-2 evolution from the BA.2.86 to JN.1 variants: unexpected consequences

Trends in Immunology, Год журнала: 2024, Номер 45(2), С. 81 - 84

Опубликована: Янв. 31, 2024

Язык: Английский

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Neutralization escape, infectivity, and membrane fusion of JN.1-derived SARS-CoV-2 SLip, FLiRT, and KP.2 variants

Cell Reports, Год журнала: 2024, Номер 43(8), С. 114520 - 114520

Опубликована: Июль 17, 2024

Highlights•SLip, FLiRT, and KP.2 are poorly neutralized by bivalent-vaccinated sera•XBB.1.5-vaccinated hamster JN.1 patient sera SLip, KP.2•S mutations R346T, L455S, F456L alter ACE2 binding neutralization epitopes•SLip, spikes exhibit less fusion processing relative to JN.1SummaryWe investigate JN.1-derived subvariants for antibodies in vaccinated individuals, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected patients, or class III monoclonal antibody S309. Compared JN.1, KP.2, especially FLiRT increased resistance BA.2.86/JN.1-wave convalescent human sera. XBB.1.5 monovalent-vaccinated robustly neutralize but have reduced efficiency SLip. All resistant S309 show decreased infectivity, cell-cell fusion, spike JN.1. Modeling reveals that L455S SLip reduce ACE2, while R346T strengthens it. These three mutations, alongside D339H, key epitopes spike, likely explaining the sensitivity of these neutralization. Our findings highlight suggest future vaccine formulations should consider as an immunogen, although current monovalent could still offer adequate protection.Graphical abstract

Язык: Английский

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Distinct patterns of SARS-CoV-2 BA.2.87.1 and JN.1 variants in immune evasion, antigenicity, and cell-cell fusion

mBio, Год журнала: 2024, Номер 15(5)

Опубликована: Апрель 9, 2024

The rapid evolution of SARS-CoV-2 variants presents a constant challenge to the global vaccination effort. In this study, we conducted comprehensive investigation into two newly emerged variants, BA.2.87.1 and JN.1, focusing on their neutralization resistance, infectivity, antigenicity, cell-cell fusion, spike processing. Neutralizing antibody (nAb) titers were assessed in diverse cohorts, including individuals who received bivalent mRNA vaccine booster, patients infected during BA.2.86/JN.1-wave, hamsters vaccinated with XBB.1.5-monovalent vaccine. We found that shows much less nAb escape from WT-BA.4/5 JN.1-wave breakthrough infection sera compared JN.1 XBB.1.5. Interestingly, is more resistant by XBB.1.5-monovalent-vaccinated hamster than BA.2.86/JN.1 XBB.1.5, but efficiently neutralized class III monoclonal S309, which largely fails neutralize BA.2.86/JN.1. Importantly, exhibits higher levels fusion activity, furin cleavage efficiency Antigenically, closer ancestral BA.2 other recently Omicron subvariants Altogether, these results highlight immune properties as well biology new underscore importance continuous surveillance informed decision-making development effective vaccines.

Язык: Английский

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Safety and Immunogenicity of the Monovalent Omicron XBB.1.5-Adapted BNT162b2 COVID-19 Vaccine in Individuals ≥12 Years Old: A Phase 2/3 Trial

Vaccines, Год журнала: 2024, Номер 12(2), С. 118 - 118

Опубликована: Янв. 24, 2024

Vaccination remains an important mitigation tool against COVID-19. We report 1-month safety and preliminary immunogenicity data from a substudy of ongoing, open-label, phase 2/3 study monovalent Omicron XBB.1.5-adapted BNT162b2 (single 30-μg dose). Healthy participants ≥12 years old (N = 412 (12–17 years, N 30; 18–55 174; >55 208)) who previously received ≥3 doses US-authorized mRNA vaccine, the most recent being BA.4/BA.5-adapted bivalent vaccine ≥150 days before vaccination, were vaccinated. Serum 50% neutralizing titers XBB.1.5, EG.5.1, BA.2.86 measured 7 1 month after vaccination in subset ≥18-year-olds 40) positive for SARS-CoV-2 at baseline. Seven-day was also evaluated matched group previous (ClinicalTrials.gov Identifier: NCT05472038). There no new signals; local reactions systemic events mostly mild to moderate severity, adverse infrequent, none led withdrawal. The induced numerically higher than robust responses all three sublineages month. These support favorable benefit-risk profile 30 μg. ClinicalTrials.gov NCT05997290

Язык: Английский

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Evolution of the SARS-CoV-2 Omicron Variants: Genetic Impact on Viral Fitness

Viruses, Год журнала: 2024, Номер 16(2), С. 184 - 184

Опубликована: Янв. 25, 2024

Over the last three years, pandemic of COVID-19 has had a significant impact on people’s lives and global economy. The incessant emergence variant strains compounded challenges associated with management COVID-19. As predominant from late 2021 to present, Omicron its sublineages, through continuous evolution, have demonstrated iterative viral fitness. comprehensive elucidation biological implications that catalyzed this evolution remains incomplete. In accordance extant research evidence, we provide review subvariants Omicron, delineating alterations in immune evasion, cellular infectivity, cross-species transmission potential. This seeks clarify underpinnings biology within SARS-CoV-2, thereby providing foundation for strategic considerations post-pandemic era

Язык: Английский

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Mutations in the SARS-CoV-2 spike receptor binding domain and their delicate balance between ACE2 affinity and antibody evasion

Protein & Cell, Год журнала: 2024, Номер 15(6), С. 403 - 418

Опубликована: Март 4, 2024

Intensive selection pressure constrains the evolutionary trajectory of SARS-CoV-2 genomes and results in various novel variants with distinct mutation profiles. Point mutations, particularly those within receptor binding domain (RBD) spike (S) protein, lead to functional alteration both engagement monoclonal antibody (mAb) recognition. Here, we review data RBD point mutations possessed by major discuss their individual effects on ACE2 affinity immune evasion. Many single amino acid substitutions epitopes crucial for evasion capacity may conversely weaken affinity. However, this weakened effect could be largely compensated specific epistatic such as N501Y, thus maintaining overall protein all variants. The predominant direction evolution lies neither promoting nor evading mAb neutralization but a delicate balance between these two dimensions. Together, interprets how efficiently resist meanwhile is maintained, emphasizing significance comprehensive assessment mutations.

Язык: Английский

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Sotrovimab: A Review of Its Efficacy against SARS-CoV-2 Variants

Viruses, Год журнала: 2024, Номер 16(2), С. 217 - 217

Опубликована: Янв. 31, 2024

Among the anti-Spike monoclonal antibodies (mAbs), S-309 derivative sotrovimab was most successful in having longest temporal window of clinical use, showing a high degree resiliency to SARS-CoV-2 evolution interrupted only by appearance BA.2.86* variant interest (VOI). This success undoubtedly reflects rational selection target highly conserved epitope coronavirus Spike proteins. We review here efficacy against different variants outpatients and inpatients, discussing both randomized controlled trials real-world evidence. Although it could not be anticipated at time its development introduction, sotrovimab's use immunocompromised individuals who harbor large populations viruses created conditions for eventual demise, as antibody viral led withdrawal due inefficacy later lineages. Despite this, based on observational data, some authorities have continued promote sotrovimab, but lack binding newer strongly argues futility use. The story highlights power modern biomedical science generate novel therapeutics while also providing cautionary tale need devise strategies minimize emergence resistance antibody-based therapeutics.

Язык: Английский

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