Imprinted SARS-CoV-2 humoral immunity induces convergent Omicron RBD evolution

Nature, Год журнала: 2022, Номер unknown

Опубликована: Дек. 19, 2022

Abstract Continuous evolution of Omicron has led to a rapid and simultaneous emergence numerous variants that display growth advantages over BA.5 (ref. 1 ). Despite their divergent evolutionary courses, mutations on receptor-binding domain (RBD) converge several hotspots. The driving force destination such sudden convergent its effect humoral immunity remain unclear. Here we demonstrate these can cause evasion neutralizing antibody drugs convalescent plasma, including those from breakthrough infection, while maintaining sufficient ACE2-binding capability. BQ.1.1.10 (BQ.1.1 + Y144del), BA.4.6.3, XBB CH.1.1 are the most antibody-evasive strains tested. To delineate origin evolution, determined escape mutation profiles neutralization activity monoclonal antibodies isolated individuals who had BA.2 infections 2,3 . Owing immune imprinting, especially infection reduced diversity binding sites increased proportions non-neutralizing clones, which, in turn, focused pressure promoted RBD. Moreover, show RBD could be accurately inferred by deep mutational scanning 4,5 , trends BA.2.75 subvariants well foreseen through constructed pseudovirus mutants. These results suggest current herd vaccine boosters may not efficiently prevent variants.

Язык: Английский

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Enhanced neutralization resistance of SARS-CoV-2 Omicron subvariants BQ.1, BQ.1.1, BA.4.6, BF.7, and BA.2.75.2

Cell Host & Microbe, Год журнала: 2022, Номер 31(1), С. 9 - 17.e3

Опубликована: Ноя. 22, 2022

Язык: Английский

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Resistance of Omicron subvariants BA.2.75.2, BA.4.6, and BQ.1.1 to neutralizing antibodies

Nature Communications, Год журнала: 2023, Номер 14(1)

Опубликована: Фев. 14, 2023

Abstract Convergent evolution of SARS-CoV-2 Omicron BA.2, BA.4, and BA.5 lineages has led to the emergence several new subvariants, including BA.2.75.2, BA.4.6. BQ.1.1. The subvariant BQ.1.1 became predominant in many countries December 2022. subvariants carry an additional often redundant set mutations spike, likely responsible for increased transmissibility immune evasion. Here, we established a viral amplification procedure easily isolate strains. We examined their sensitivity 6 therapeutic monoclonal antibodies (mAbs) 72 sera from Pfizer BNT162b2-vaccinated individuals, with or without BA.1/BA.2 breakthrough infection. Ronapreve (Casirivimab Imdevimab) Evusheld (Cilgavimab Tixagevimab) lose antiviral efficacy against BA.2.75.2 BQ.1.1, whereas Xevudy (Sotrovimab) remaine weakly active. is also resistant Bebtelovimab. Neutralizing titers triply vaccinated individuals are low undetectable 4 months after boosting. A infection increases these titers, which remains about 18-fold lower than BA.1. Reciprocally, more efficiently neutralization BA.2.75.2. Thus, trajectory novel facilitates spread immunized populations raises concerns most available mAbs.

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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Broadly neutralizing anti-S2 antibodies protect against all three human betacoronaviruses that cause deadly disease

Immunity, Год журнала: 2023, Номер 56(3), С. 669 - 686.e7

Опубликована: Фев. 16, 2023

Pan-betacoronavirus neutralizing antibodies may hold the key to developing broadly protective vaccines against novel pandemic coronaviruses and more effectively respond SARS-CoV-2 variants. The emergence of Omicron subvariants illustrates limitations solely targeting receptor-binding domain (RBD) spike (S) protein. Here, we isolated a large panel (bnAbs) from recovered-vaccinated donors, which targets conserved S2 region in betacoronavirus fusion machinery. Select bnAbs showed broad vivo protection all three deadly betacoronaviruses, SARS-CoV-1, SARS-CoV-2, MERS-CoV, have spilled over into humans past two decades. Structural studies these delineated molecular basis for their reactivity revealed common antibody features targetable by vaccination strategies. These provide new insights opportunities antibody-based interventions pan-betacoronavirus vaccines.

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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Immune evasion, infectivity, and fusogenicity of SARS-CoV-2 BA.2.86 and FLip variants

Cell, Год журнала: 2024, Номер 187(3), С. 585 - 595.e6

Опубликована: Янв. 8, 2024

Evolution of SARS-CoV-2 requires the reassessment current vaccine measures. Here, we characterized BA.2.86 and XBB-derived variant FLip by investigating their neutralization alongside D614G, BA.1, BA.2, BA.4/5, XBB.1.5, EG.5.1 sera from 3-dose-vaccinated bivalent-vaccinated healthcare workers, XBB.1.5-wave-infected first responders, monoclonal antibody (mAb) S309. We assessed biology spikes measuring viral infectivity membrane fusogenicity. is less immune evasive compared to other XBB variants, consistent with antigenic distances. Importantly, distinct mAb S309 was unable neutralize BA.2.86, likely due a D339H mutation based on modeling. had relatively high fusogenicity in CaLu-3 cells but low fusion 293T-ACE2 some suggesting potentially different conformational stability spike. Overall, our study underscores importance surveillance need for updated COVID-19 vaccines.

Язык: Английский

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Rational identification of potent and broad sarbecovirus-neutralizing antibody cocktails from SARS convalescents

Cell Reports, Год журнала: 2022, Номер 41(12), С. 111845 - 111845

Опубликована: Дек. 1, 2022

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron sublineages have escaped most receptor-binding domain (RBD)-targeting therapeutic neutralizing antibodies (NAbs), which proves that previous NAb drug screening strategies are deficient against the fast-evolving SARS-CoV-2. Better broad candidate selection methods needed. Here, we describe a rational approach for identifying RBD-targeting SARS-CoV-2 cocktails. Based on high-throughput epitope determination, propose drugs should target non-immunodominant RBD epitopes to avoid herd-immunity-directed escape mutations. Also, their interacting antigen residues focus sarbecovirus conserved sites and associate with critical viral functions, making antibody-escaping mutations less likely appear. Following these criteria, featured non-competing antibody cocktail, SA55+SA58, is identified from large collection of NAbs isolated SARS-CoV-2-vaccinated SARS convalescents. SA55+SA58 potently neutralizes ACE2-utilizing sarbecoviruses, including circulating variants, could serve as prophylactics offer long-term protection, especially individuals who immunocompromised or high-risk comorbidities.

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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Epidemiology, clinical presentation, pathophysiology, and management of long COVID: an update

Molecular Psychiatry, Год журнала: 2023, Номер 28(10), С. 4056 - 4069

Опубликована: Июль 25, 2023

Язык: Английский

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