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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Enhanced transmissibility, infectivity, and immune resistance of the SARS-CoV-2 omicron XBB.1.5 variant

The Lancet Infectious Diseases, Год журнала: 2023, Номер 23(3), С. 280 - 281

Опубликована: Фев. 1, 2023

Язык: Английский

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Neutralization, effector function and immune imprinting of Omicron variants

Nature, Год журнала: 2023, Номер 621(7979), С. 592 - 601

Опубликована: Авг. 30, 2023

Abstract Currently circulating SARS-CoV-2 variants have acquired convergent mutations at hot spots in the receptor-binding domain 1 (RBD) of spike protein. The effects these on viral infection and transmission efficacy vaccines therapies remains poorly understood. Here we demonstrate that recently emerged BQ.1.1 XBB.1.5 bind host ACE2 with high affinity promote membrane fusion more efficiently than earlier Omicron variants. Structures BQ.1.1, XBB.1 BN.1 RBDs bound to fragment antigen-binding region S309 antibody (the parent for sotrovimab) human explain preservation binding through conformational selection, altered recognition immune evasion. We show sotrovimab binds avidly all variants, promotes Fc-dependent effector functions protects mice challenged hamsters XBB.1.5. Vaccine-elicited plasma antibodies cross-react trigger against current despite a reduced neutralizing activity, suggesting mechanism protection disease, exemplified by S309. Cross-reactive RBD-directed memory B cells remained dominant even after two exposures spikes, underscoring role persistent imprinting.

Язык: Английский

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The rapid rise of SARS‐CoV‐2 Omicron subvariants with immune evasion properties: XBB.1.5 and BQ.1.1 subvariants

MedComm, Год журнала: 2023, Номер 4(2)

Опубликована: Март 15, 2023

As the fifth variant of concern SARS-CoV-2 virus, Omicron (B.1.1.529) has quickly become dominant type among previous circulating variants worldwide. During wave, several subvariants have emerged, with some exhibiting greater infectivity and immune evasion, accounting for their fast spread across many countries. Recently, two subvariants, BQ.1 XBB lineages, including BQ.1.1, XBB.1, XBB.1.5, a global public health issue given ability to escape from therapeutic monoclonal antibodies herd immunity induced by prior coronavirus disease 2019 (COVID-19) vaccines, boosters, infection. In this respect, which been established harbor rare mutation F486P, demonstrates superior transmissibility compared other emerged as strain in This review provides comprehensive overview epidemiological features, spike mutations, evasion lineages. We expounded on mechanisms underlying mutations neutralizing vaccinated or convalescent COVID-19 individuals (mAbs) proposed strategies prevention against sublineages.

Язык: Английский

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Antiviral and bivalent vaccine efficacy against an omicron XBB.1.5 isolate

The Lancet Infectious Diseases, Год журнала: 2023, Номер 23(4), С. 402 - 403

Опубликована: Фев. 9, 2023

Язык: Английский

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Angiotensin-converting enzyme 2—at the heart of the COVID-19 pandemic

Cell, Год журнала: 2023, Номер 186(5), С. 906 - 922

Опубликована: Фев. 2, 2023

ACE2 is the indispensable entry receptor for SARS-CoV and SARS-CoV-2. Because of COVID-19 pandemic, it has become one most therapeutically targeted human molecules in biomedicine. serves two fundamental physiological roles: as an enzyme, alters peptide cascade balance; a chaperone, controls intestinal amino acid uptake. ACE2's tissue distribution, affected by co-morbidities sex, explains broad tropism coronaviruses clinical manifestations SARS COVID-19. ACE2-based therapeutics provide universal strategy to prevent treat SARS-CoV-2 infections, applicable all variants other emerging zoonotic exploiting their cellular receptor.

Язык: Английский

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Coronavirus variant XBB.1.5 rises in the United States — is it a global threat?

Nature, Год журнала: 2023, Номер 613(7943), С. 222 - 223

Опубликована: Янв. 9, 2023

Язык: Английский

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Immune evasion and membrane fusion of SARS-CoV-2 XBB subvariants EG.5.1 and XBB.2.3

Emerging Microbes & Infections, Год журнала: 2023, Номер 12(2)

Опубликована: Окт. 11, 2023

Immune evasion by SARS-CoV-2 paired with immune imprinting from monovalent mRNA vaccines has resulted in attenuated neutralizing antibody responses against Omicron subvariants. In this study, we characterized two new XBB variants rising circulation - EG.5.1 and XBB.2.3, for their neutralization syncytia formation. We determined the titers sera of individuals that received a bivalent vaccine booster, BA.4/5-wave infection, or XBB.1.5-wave infection. Bivalent vaccination-induced antibodies neutralized ancestral D614G efficiently, but to much less extent, XBB.2.3 variants. fact, enhanced escape appeared be driven its key defining mutation XBB.1.5-F456L. Notably, infection BA.4/5 XBB.1.5 afforded little, if any, EG.5.1, previous especially unvaccinated individuals, average near limit detection. Additionally, investigated infectivity, fusion activity, processing variant spikes HEK293T-ACE2 CaLu-3 cells found no significant differences compared earlier Overall, our findings highlight continued subvariants and, more importantly, need reformulate include better protection.

Язык: Английский

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SARS-CoV-2 Omicron variants: burden of disease, impact on vaccine effectiveness and need for variant-adapted vaccines

Frontiers in Immunology, Год журнала: 2023, Номер 14

Опубликована: Май 23, 2023

The highly transmissible Omicron (B.1.1.529) variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first detected in late 2021. Initial waves were primarily made up sub-lineages BA.1 and/or BA.2, BA.4, and BA.5 subsequently became dominant mid-2022, several descendants these have since emerged. infections generally caused less disease on average than those by earlier variants concern healthy adult populations, at least, part, due to increased population immunity. Nevertheless, healthcare systems many countries, particularly with low immunity, been overwhelmed unprecedented surges prevalence during waves. Pediatric admissions also higher compared previous concern. All exhibit partial escape from wild-type (Wuhan-Hu 1) spike-based vaccine-elicited neutralizing antibodies, more enhanced immuno-evasive properties emerging over time. Evaluating vaccine effectiveness (VE) against has become challenging a complex background varying coverage, platforms, prior infection rates, hybrid Original messenger RNA booster doses substantially improved VE or BA.2 symptomatic disease. However, protection waned, reductions months after administration. While original CD8 + CD4 T-cell responses cross-recognize sub-lineages, thereby retaining outcomes, variant-adapted vaccines are required expand the breadth B-cell improve durability protection. Variant-adapted rolled out 2022 increase overall antigenically aligned immune mechanisms.

Язык: Английский

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Emergence and antibody evasion of BQ, BA.2.75 and SARS-CoV-2 recombinant sub-lineages in the face of maturing antibody breadth at the population level

EBioMedicine, Год журнала: 2023, Номер 90, С. 104545 - 104545

Опубликована: Март 30, 2023

Язык: Английский

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