SARS-CoV-2 Omicron is an immune escape variant with an altered cell entry pathway

Nature Microbiology, Journal Year: 2022, Volume and Issue: 7(8), P. 1161 - 1179

Published: July 7, 2022

Vaccines based on the spike protein of SARS-CoV-2 are a cornerstone public health response to COVID-19. The emergence hypermutated, increasingly transmissible variants concern (VOCs) threaten this strategy. Omicron (B.1.1.529), fifth VOC be described, harbours multiple amino acid mutations in spike, half which lie within receptor-binding domain. Here we demonstrate substantial evasion neutralization by BA.1 and BA.2 vitro using sera from individuals vaccinated with ChAdOx1, BNT162b2 mRNA-1273. These data were mirrored reduction real-world vaccine effectiveness that was partially restored booster vaccination. did not induce cell syncytia favoured TMPRSS2-independent endosomal entry pathway, these phenotypes mapping distinct regions protein. Impaired fusion determined domain, while mapped S2 Such marked changes antigenicity replicative biology may underlie rapid global spread altered pathogenicity variant.

Language: Английский

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

Signal Transduction and Targeted Therapy, Journal Year: 2022, Volume and Issue: 7(1)

Published: April 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.

Language: 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, Journal Year: 2022, Volume and Issue: 32(5)

Published: July 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.

Language: Английский

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Advances in COVID-19 mRNA vaccine development

Signal Transduction and Targeted Therapy, Journal Year: 2022, Volume and Issue: 7(1)

Published: March 23, 2022

Abstract To date, the coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome 2 (SARS-CoV-2) has determined 399,600,607 cases and 5,757,562 deaths worldwide. COVID-19 is a serious threat to human health globally. The World Health Organization (WHO) declared pandemic major public emergency. Vaccination most effective economical intervention for controlling spread of epidemics, consequently saving lives protecting population. Various techniques have been employed in development vaccines. Among these, messenger RNA (mRNA) vaccine drawing increasing attention owing its great application prospects advantages, which include short cycle, easy industrialization, simple production process, flexibility respond new variants, capacity induce better immune response. This review summarizes current knowledge on structural characteristics, antigen design strategies, delivery systems, industrialization potential, quality control, latest clinical trials real-world data mRNA vaccines as well technology. Current challenges future directions preventive infectious diseases are also discussed.

Language: Английский

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Immune boosting by B.1.1.529 ( Omicron) depends on previous SARS-CoV-2 exposure

Science, Journal Year: 2022, Volume and Issue: 377(6603)

Published: June 14, 2022

The Omicron, or Pango lineage B.1.1.529, variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) carries multiple spike mutations with high transmissibility and partial neutralizing antibody (nAb) escape. Vaccinated individuals show protection against disease, often attributed to primed cellular immunity. We investigated T B cell immunity B.1.1.529 in triple BioNTech BNT162b2 messenger RNA-vaccinated health care workers (HCWs) different SARS-CoV-2 infection histories. previous variants concern was enhanced triple-vaccinated individuals, but the magnitude responses protein reduced. Immune imprinting by earlier B.1.1.7 (Alpha) resulted less durable binding B.1.1.529. Previously infection-naïve HCWs who became infected during wave showed reduced nAb potency itself. Previous Wuhan Hu-1 abrogated recognition any cross-reactive on

Language: Английский

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Estimated Effectiveness of COVID-19 Vaccines Against Omicron or Delta Symptomatic Infection and Severe Outcomes

JAMA Network Open, Journal Year: 2022, Volume and Issue: 5(9), P. e2232760 - e2232760

Published: Sept. 22, 2022

The incidence of SARS-CoV-2 infection, including among individuals who have received 2 doses COVID-19 vaccine, increased substantially following the emergence Omicron variant in Ontario, Canada. Understanding estimated effectiveness or 3 vaccine against outcomes associated with and Delta infections may aid decision-making at individual population levels.To estimate (VE) symptomatic due to variants severe (hospitalization death) these infections.This test-negative case-control study used linked provincial databases for laboratory testing, reportable disease, vaccination, health administration Participants were aged 18 years older had symptoms tested between December 6 26, 2021.Receipt time since last dose.The main infection infection. Multivariable logistic regression was by latest dose compared no vaccination. Estimated VE calculated using formula = (1 - [adjusted odds ratio]) × 100%.Of 134 435 total participants, 16 087 Omicron-positive cases (mean [SD] age, 36.0 [14.1] years; 8249 [51.3%] female), 4261 Delta-positive 44.2 [16.8] 2199 [51.6%] 114 controls 42.0 [16.5] 67 884 [59.5%] female). decreased from 89% (95% CI, 86%-92%) 7 59 days after a second 80% 74%-84%) 240 more but 97% 96%-98%) third dose. 36% 24%-45%) 1% -8% 10%) 180 longer, dose, it 61% 56%-65%). high both (99%; 95% 98%-99%) (95%; 87%-98%).In this study, contrast modest short term better maintained outcomes. A improved variants. Preventing potential future require tools beyond currently available vaccines.

Language: Английский

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Respiratory mucosal immunity against SARS-CoV-2 after mRNA vaccination

Science Immunology, Journal Year: 2022, Volume and Issue: 7(76)

Published: July 19, 2022

SARS-CoV-2 mRNA vaccination induces robust humoral and cellular immunity in the circulation; however, it is currently unknown whether elicits effective immune responses respiratory tract, particularly against variants of concern (VOCs), including Omicron. We compared S-specific total neutralizing antibody responses, B T cell immunity, bronchoalveolar lavage fluid (BAL) blood COVID-19-vaccinated individuals hospitalized patients. Vaccinated had significantly lower levels D614G, Delta (B.1.617.2), Omicron BA.1.1 BAL with COVID-19 convalescents despite blood. Furthermore, induced circulating but contrast to convalescents, these were absent vaccinated individuals. Using a mouse immunization model, we demonstrated that systemic alone weak mucosal especially mice; combination plus adenovirus-S strong not only ancestral virus also variant. Together, our study supports contention current vaccines are highly severe disease development, likely through recruiting during reinfection, offer limited protection breakthrough infection, by sublineage. Hence, booster needed establish sterilizing tract SARS-CoV-2, infection sublineage future VOCs.

Language: Английский

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mRNA-1273 or mRNA-Omicron boost in vaccinated macaques elicits similar B cell expansion, neutralizing responses, and protection from Omicron

Cell, Journal Year: 2022, Volume and Issue: 185(9), P. 1556 - 1571.e18

Published: March 25, 2022

Language: Английский

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COVID-19 mRNA vaccines: Platforms and current developments

Molecular Therapy, Journal Year: 2022, Volume and Issue: 30(5), P. 1850 - 1868

Published: Feb. 19, 2022

Since the first successful application of messenger ribonucleic acid (mRNA) as a vaccine agent in preclinical study nearly 30 years ago, numerous advances have been made field mRNA therapeutic technologies. This research uncovered unique favorable characteristics vaccines, including their ability to give rise non-toxic, potent immune responses and potential design upscale them rapidly, making excellent candidates during coronavirus disease 2019 (COVID-19) pandemic. Indeed, two vaccines against COVID-19 receive accelerated regulatory authorization were nucleoside-modified which showed more than 90% protective efficacy symptomatic severe acute respiratory syndrome 2 (SARS-CoV-2) infection alongside tolerable safety profiles pivotal phase III clinical trials. Real-world evidence following deployment global vaccination campaigns utilizing has bolstered trial further illustrated that this technology can be used safely effectively combat COVID-19. unprecedented success also emphasized broader new drug class, not only for other infectious diseases, but indications, such cancer inherited diseases. review presents brief history current status development four platforms, unmodified mRNA, circular RNA, self-amplifying well an overview recent progress vaccines. We discuss anticipated challenges these technologies, may important future endeavors applications.

Language: Английский

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Omicron BA.1 breakthrough infection drives cross-variant neutralization and memory B cell formation against conserved epitopes

Science Immunology, Journal Year: 2022, Volume and Issue: 7(75)

Published: June 2, 2022

Omicron is the evolutionarily most distinct severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant of concern (VOC) to date. We report that BA.1 breakthrough infection in BNT162b2-vaccinated individuals resulted strong neutralizing activity against BA.1, BA.2, and previous SARS-CoV-2 VOCs but not sublineages BA.4 BA.5. induced a robust recall response, primarily expanding memory B (B

Language: Английский

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