SARS-CoV-2 variant biology: immune escape, transmission and fitness

Nature Reviews Microbiology, Год журнала: 2023, Номер unknown

Опубликована: Янв. 18, 2023

In late 2020, after circulating for almost a year in the human population, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) exhibited major step change its adaptation to humans. These highly mutated forms of SARS-CoV-2 had enhanced rates transmission relative previous variants and were termed 'variants concern' (VOCs). Designated Alpha, Beta, Gamma, Delta Omicron, VOCs emerged independently from one another, turn each rapidly became dominant, regionally or globally, outcompeting variants. The success VOC previously dominant variant was enabled by altered intrinsic functional properties virus and, various degrees, changes antigenicity conferring ability evade primed immune response. increased fitness associated with is result complex interplay biology context changing immunity due both vaccination prior infection. this Review, we summarize literature on transmissibility variants, role mutations at furin spike cleavage site non-spike proteins, potential importance recombination success, evolution T cells, innate population immunity. shows complicated relationship among antigenicity, virulence, which has unpredictable implications future trajectory disease burden COVID-19.

Язык: Английский

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Alarming antibody evasion properties of rising SARS-CoV-2 BQ and XBB subvariants

Cell, Год журнала: 2022, Номер 186(2), С. 279 - 286.e8

Опубликована: Дек. 14, 2022

The BQ and XBB subvariants of SARS-CoV-2 Omicron are now rapidly expanding, possibly due to altered antibody evasion properties deriving from their additional spike mutations. Here, we report that neutralization BQ.1, BQ.1.1, XBB, XBB.1 by sera vaccinees infected persons was markedly impaired, including individuals boosted with a WA1/BA.5 bivalent mRNA vaccine. Titers against were lower 13- 81-fold 66- 155-fold, respectively, far beyond what had been observed date. Monoclonal antibodies capable neutralizing the original variant largely inactive these new subvariants, responsible individual mutations identified. These found have similar ACE2-binding affinities as predecessors. Together, our findings indicate present serious threats current COVID-19 vaccines, render all authorized antibodies, may gained dominance in population because advantage evading antibodies.

Язык: Английский

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Antibody evasion by SARS-CoV-2 Omicron subvariants BA.2.12.1, BA.4 and BA.5

Nature, Год журнала: 2022, Номер 608(7923), С. 603 - 608

Опубликована: Июль 5, 2022

Abstract SARS-CoV-2 Omicron subvariants BA.2.12.1 and BA.4/5 have surged notably to become dominant in the United States South Africa, respectively 1,2 . These new carrying further mutations their spike proteins raise concerns that they may evade neutralizing antibodies, thereby compromising efficacy of COVID-19 vaccines therapeutic monoclonals. We now report findings from a systematic antigenic analysis these surging subvariants. is only modestly (1.8-fold) more resistant sera vaccinated boosted individuals than BA.2. However, substantially (4.2-fold) thus likely lead vaccine breakthrough infections. Mutation at residue L452 found both facilitates escape some antibodies directed so-called class 2 3 regions receptor-binding domain The F486V mutation certain 1 but compromises affinity for viral receptor. R493Q reversion mutation, however, restores receptor consequently fitness BA.4/5. Among authorized clinical use, bebtelovimab retains full potency against lineage continues evolve, successively yielding are not transmissible also evasive antibodies.

Язык: Английский

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A Bivalent Omicron-Containing Booster Vaccine against Covid-19

New England Journal of Medicine, Год журнала: 2022, Номер 387(14), С. 1279 - 1291

Опубликована: Сен. 16, 2022

The safety and immunogenicity of the bivalent omicron-containing mRNA-1273.214 booster vaccine are not known.In this ongoing, phase 2-3 study, we compared 50-μg (25 μg each ancestral Wuhan-Hu-1 omicron B.1.1.529 [BA.1] spike messenger RNAs) with previously authorized mRNA-1273 booster. We administered or as a second in adults who had received two-dose (100-μg) primary series first (50-μg) dose (≥3 months earlier). objectives were to assess safety, reactogenicity, at 28 days after dose.Interim results presented. Sequential groups participants 50 (437 participants) (377 dose. median time between boosters was similar for (136 days) (134 days). In no previous severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, geometric mean titers neutralizing antibodies against BA.1 variant 2372.4 (95% confidence interval [CI], 2070.6 2718.2) receipt 1473.5 CI, 1270.8 1708.4) addition, elicited 727.4 632.8 836.1) 492.1 431.1 561.9), respectively, BA.4 BA.5 (BA.4/5), also higher binding antibody responses multiple other variants (alpha, beta, gamma, delta) than Safety reactogenicity two vaccines. Vaccine effectiveness assessed study; an exploratory analysis, SARS-CoV-2 infection occurred 11 9 booster.The that superior those mRNA-1273, without evident concerns. (Funded by Moderna; ClinicalTrials.gov number, NCT04927065.).

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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Evolution of the SARS‐CoV‐2 omicron variants BA.1 to BA.5: Implications for immune escape and transmission

Reviews in Medical Virology, Год журнала: 2022, Номер 32(5)

Опубликована: Июль 20, 2022

Abstract The first dominant SARS‐CoV‐2 Omicron variant BA.1 harbours 35 mutations in its Spike protein from the original that emerged late 2019. Soon after discovery, rapidly to become worldwide and has since evolved into several variants. is of major public health concern owing high infectivity antibody evasion. This review article examines theories have been proposed on evolution including zoonotic spillage, infection immunocompromised individuals cryptic spread community without being diagnosed. Added complexity Omicron's are multiple reports recombination events occurring between co‐circulating variants with Delta other such as XE. Current literature suggests combination novel resulted having higher than Wuhan‐Hu‐1 variant. However, severity believed be less reduced syncytia formation lower multiplication human lung tissue. Perhaps most challenging studies indicate efficacy available vaccines against (8–127 times reduction) compared administration booster vaccine, however, compensates reduction improves by 12–35 fold. Concerningly though, broadly neutralising monoclonal antibodies, those approved FDA for therapeutic use previous variants, mostly ineffective exception Sotrovimab recent suggest BA.2 also resistant Sotrovimab. Currently two new BA.4 BA.5 emerging reported more transmissible immunity generated antibodies. As will likely continue emerge it important evolution, biological consequences mutations, existing well understood.

Язык: Английский

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Covid-19 Vaccines — Immunity, Variants, Boosters

New England Journal of Medicine, Год журнала: 2022, Номер 387(11), С. 1011 - 1020

Опубликована: Авг. 31, 2022

T he coronavirus disease 2019 (Covid-19) pandemic has claimed an estimated 15 million lives, including more than 1 lives in the United States alone.The rapid development of multiple Covid-19 vaccines been a triumph biomedical research, and billions vaccine doses have administered worldwide.Challenges facing field include inequitable distribution, hesitancy, waning immunity, emergence highly transmissible viral variants that partially escape antibodies.This review summarizes current state knowledge about immune responses to importance both humoral cellular immunity for durable protection against severe disease. A nti v ir l Immunit yThe system is broadly divided into innate adaptive systems.Innate are first line defense viruses rapidly triggered when pattern-recognition receptors, such as toll-like recognize pathogen-associated molecular patterns.Innate antiviral includes secretion type I interferons, cytokines, certain responses, neutrophils, monocytes macrophages, dendritic cells, natural killer cells. Adaptive second viruses, involve antigen-specific recognition epitopes.Adaptive two complementary branches system: immunity.Humoral acute respiratory syndrome 2 (SARS-CoV-2) antibodies bind SARS-CoV-2 spike protein either neutralize virus or eliminate it through other effector mechanisms. 2,3ellular virus-specific B cells which provide long-term immunologic memory expand on reexposure antigen.B produce antibodies, CD8+ directly virally infected CD4+ help support responses.5][6][7] For variant largely escapes neutralizing may be particularly important longterm

Язык: Английский

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SARS-CoV-2 viral load and shedding kinetics

Nature Reviews Microbiology, Год журнала: 2022, Номер unknown

Опубликована: Дек. 2, 2022

Язык: Английский

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Outbreak.info genomic reports: scalable and dynamic surveillance of SARS-CoV-2 variants and mutations

Nature Methods, Год журнала: 2023, Номер 20(4), С. 512 - 522

Опубликована: Фев. 23, 2023

Язык: Английский

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Broadly neutralizing antibodies to SARS-CoV-2 and other human coronaviruses

Nature reviews. Immunology, Год журнала: 2022, Номер 23(3), С. 189 - 199

Опубликована: Сен. 27, 2022

Язык: Английский

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