BA.2.12.1, BA.4 and BA.5 escape antibodies elicited by Omicron infection

Nature, Год журнала: 2022, Номер 608(7923), С. 593 - 602

Опубликована: Июнь 17, 2022

Abstract Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron sublineages BA.2.12.1, BA.4 and BA.5 exhibit higher transmissibility than the BA.2 lineage 1 . The receptor binding immune-evasion capability of these recently emerged variants require immediate investigation. Here, coupled with structural comparisons spike proteins, we show that (BA.4 are hereafter referred collectively to as BA.4/BA.5) similar affinities for angiotensin-converting enzyme (ACE2) receptor. Of note, BA.2.12.1 BA.4/BA.5 display increased evasion neutralizing antibodies compared against plasma from triple-vaccinated individuals or who developed a BA.1 infection after vaccination. To delineate underlying antibody-evasion mechanism, determined escape mutation profiles , epitope distribution 3 Omicron-neutralization efficiency 1,640 directed receptor-binding domain viral protein, including 614 isolated people had recovered infection. vaccination predominantly recalls humoral immune memory ancestral (hereafter wild-type (WT)) SARS-CoV-2 protein. resulting elicited could neutralize both WT enriched on epitopes do not bind ACE2. However, most cross-reactive evaded by mutants L452Q, L452R F486V. can also induce new clones BA.1-specific potently BA.1. Nevertheless, largely owing D405N F486V mutations, react weakly pre-Omicron variants, exhibiting narrow neutralization breadths. therapeutic bebtelovimab 4 cilgavimab 5 effectively BA.4/BA.5, whereas S371F, R408S mutations undermine broadly sarbecovirus-neutralizing antibodies. Together, our results indicate may evolve evade immunity infection, suggesting BA.1-derived vaccine boosters achieve broad-spectrum protection variants.

Язык: Английский

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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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SARS-CoV-2 Omicron variant: recent progress and future perspectives

Signal Transduction and Targeted Therapy, Год журнала: 2022, Номер 7(1)

Опубликована: Апрель 28, 2022

Abstract Since the outbreak of coronavirus disease 2019 (COVID-19) pandemic, there have been a few variants severe acute respiratory syndrome 2 (SARS-CoV-2), one which is Omicron variant (B.1.1.529). The most mutated SARS-CoV-2 variant, and its high transmissibility immune evasion ability raised global concerns. Owing to enhanced transmissibility, has rapidly replaced Delta as dominant in several regions. However, recent studies shown that exhibits reduced pathogenicity due altered cell tropism. In addition, significant resistance neutralizing activity vaccines, convalescent serum, antibody therapies. present review, advances molecular clinical characteristics infectivity, pathogenicity, was summarized, potential therapeutic applications response infection were discussed. Furthermore, we highlighted future waves strategies end pandemic.

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

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2022, Номер unknown

Опубликована: Сен. 16, 2022

Abstract Continuous evolution of Omicron has led to a rapid and simultaneous emergence numerous variants that display growth advantages over BA. 5. Despite their divergent evolutionary courses, mutations on receptor-binding domain (RBD) converge several hotspots. The driving force destination such convergent its impact humoral immunity remain unclear. Here, we demonstrate these can cause striking evasion neutralizing antibody (NAb) drugs convalescent plasma, including those from BA.5 breakthrough infection, while maintaining sufficient ACE2 binding capability. BQ.1.1.10, BA.4.6.3, XBB, CH. 1.1 are the most antibody-evasive strain tested, even exceeding SARS-CoV-1 level. To delineate origin evolution, determined escape mutation profiles neutralization activity monoclonal antibodies (mAbs) isolated BA.2 breakthrough-infection convalescents. Importantly, due immune imprinting, especially infection caused significant reductions in epitope diversity NAbs increased proportion non-neutralizing mAbs, which turn concentrated pressure promoted evolution. Moreover, showed RBD could be accurately inferred by integrated deep mutational scanning (DMS) profiles, trends BA.2.75/BA.5 subvariants well-simulated through constructed pseudovirus mutants. Together, our results suggest current herd vaccine boosters may not provide good protection against infection. Broad-spectrum SARS-CoV-2 vaccines NAb development should highly prioritized, mutants help examine effectiveness advance.

Язык: Английский

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A Detailed Overview of SARS-CoV-2 Omicron: Its Sub-Variants, Mutations and Pathophysiology, Clinical Characteristics, Immunological Landscape, Immune Escape, and Therapies

Viruses, Год журнала: 2023, Номер 15(1), С. 167 - 167

Опубликована: Янв. 5, 2023

The COVID-19 pandemic has created significant concern for everyone. Recent data from many worldwide reports suggest that most infections are caused by the Omicron variant and its sub-lineages, dominating all previously emerged variants. numerous mutations in Omicron’s viral genome sub-lineages attribute it a larger amount of fitness, owing to alteration transmission pathophysiology virus. With rapid change structure, sub-variants, namely BA.1, BA.2, BA.3, BA.4, BA.5, dominate community with an ability escape neutralization efficiency induced prior vaccination or infections. Similarly, several recombinant sub-variants Omicron, XBB, XBD, XBF, etc., have emerged, which better understanding. This review mainly entails changes due having higher number mutations. binding affinity, cellular entry, disease severity, infection rates, importantly, immune evading potential them discussed this review. A comparative analysis Delta other variants evolved before gives readers in-depth understanding landscape infection. Furthermore, discusses range abilities possessed approved antiviral therapeutic molecules neutralizing antibodies functional against sub-variants. evolution is causing infections, but broader aspect their not been explored. Thus, scientific should adopt elucidative approach obtain clear idea about recently including variants, so effective vaccines drugs can be achieved. This, turn, will lead drop cases and, finally, end pandemic.

Язык: Английский

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Omicron (BA.1) and sub‐variants (BA.1.1, BA.2, and BA.3) of SARS‐CoV‐2 spike infectivity and pathogenicity: A comparative sequence and structural‐based computational assessment

Journal of Medical Virology, Год журнала: 2022, Номер 94(10), С. 4780 - 4791

Опубликована: Июнь 10, 2022

The Omicron variant of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has now spread throughout world. We used computational tools to assess spike infectivity, transmission, and pathogenicity (BA.1) sub-variants (BA.1.1, BA.2, BA.3) in this study. BA.1 39 mutations, BA.1.1 40 BA.2 31 BA.3 34 with 21 shared mutations between all. observed 11 common Omicron's receptor-binding domain (RBD) sub-variants. In analysis, Y505H, N786K, T95I, N211I, N856K, V213R omicron are predicted be deleterious. Due major effect characterizing RBD, we found that had a higher positive electrostatic surface potential. This could increase interaction RBD negative potential human angiotensin-converting enzyme (hACE2). affinity for hACE2 increased transmission when compared wild-type (WT). Negative N-terminal (NTD) protein value indicates binds receptors less efficiently than WT. Given at least one receptor is highly expressed lung bronchial cells, NTD factors contributing why thought harmful lower tract. Among sub-lineages, have BA.1.1. mutated residues (K478), (R400, R490, R495), (R397 H499) formation new salt bridges hydrogen bonds. sub-variant Receptor-binding Motif (RBM) such as Q493R, N501Y, Q498, T478K, Y505H all contribute significantly binding ACE2. Interactions 493, 496, 498, 501 seem restore ACE2 effectiveness lost due other like K417N.

Язык: Английский

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Tracking SARS-CoV-2 Omicron diverse spike gene mutations identifies multiple inter-variant recombination events

Signal Transduction and Targeted Therapy, Год журнала: 2022, Номер 7(1)

Опубликована: Апрель 26, 2022

Abstract The current pandemic of COVID-19 is fueled by more infectious emergent Omicron variants. Ongoing concerns variants include possible recombinants, as genome recombination an important evolutionary mechanism for the emergence and re-emergence human viral pathogens. In this study, we identified diverse events between two major subvariants (BA.1 BA.2) other concern (VOCs) interest (VOIs), suggesting that co-infection subsequent play roles in ongoing evolution SARS-CoV-2. Through scanning high-quality completed spike gene sequences, 18 core mutations BA.1 (frequency >99%) 27 BA.2 (nine than BA.1) were identified, which 15 are specific to Omicron. share nine common amino acid (three protein with most VOCs, a origin from these VOCs. There three Alpha-related BA.2, phylogenetically closer Alpha Revertant found some dominant >95%) BA.1. Most notably, multiple characteristic Delta have been also “Deltacron”-like Variants isolated since November 11, 2021 South Africa, implies occurring Monitoring evolving SARS-CoV-2 genomes especially critically recognition abrupt changes attributes including its epitopes may call vaccine modifications.

Язык: Английский

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Molecular basis of receptor binding and antibody neutralization of Omicron

Nature, Год журнала: 2022, Номер 604(7906), С. 546 - 552

Опубликована: Фев. 28, 2022

Язык: Английский

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Structural diversity of the SARS-CoV-2 Omicron spike

Molecular Cell, Год журнала: 2022, Номер 82(11), С. 2050 - 2068.e6

Опубликована: Март 25, 2022

Язык: Английский

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