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

Nature Reviews Microbiology, Journal Year: 2023, Volume and Issue: unknown

Published: Jan. 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.

Language: Английский

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Low neutralization of SARS-CoV-2 Omicron BA.2.75.2, BQ.1.1 and XBB.1 by parental mRNA vaccine or a BA.5 bivalent booster

Nature Medicine, Journal Year: 2022, Volume and Issue: 29(2), P. 344 - 347

Published: Dec. 6, 2022

Language: Английский

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COVID-19 vaccine development: milestones, lessons and prospects

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

Published: May 3, 2022

Abstract With the constantly mutating of SARS-CoV-2 and emergence Variants Concern (VOC), implementation vaccination is critically important. Existing vaccines mainly include inactivated, live attenuated, viral vector, protein subunit, RNA, DNA, virus-like particle (VLP) vaccines. Viral vector vaccines, subunit mRNA may induce additional cellular or humoral immune regulations, including Th cell responses germinal center responses, form relevant memory cells, greatly improving their efficiency. However, some be associated with complications like thrombocytopenia myocarditis, raising concerns about safety these COVID-19 Here, we systemically assess efficacy possible different effects on pregnant women, elderly, people diseases acquired immunodeficiency syndrome (AIDS), transplant recipients, cancer patients. Based current analysis, governments agencies are recommended to continue advance vaccine immunization process. Simultaneously, special attention should paid health status timely treatment complications, development, ensuring lives In addition, available measures such as mix-and-match vaccination, developing new nanoparticle optimizing adjuvant improve could considered.

Language: Английский

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Covid‐19 vaccines and variants of concern: A review

Reviews in Medical Virology, Journal Year: 2021, Volume and Issue: 32(4)

Published: Nov. 9, 2021

Abstract Since the outbreak of coronavirus disease 2019 (Covid‐19) in December 2019, caused by severe acute respiratory syndrome 2 (SARS‐CoV‐2), number confirmed infections has risen to more than 242 million worldwide, with nearly 5 deaths. Currently, nine Covid‐19 vaccine candidates based on original Wuhan‐Hu‐1 strain are at forefront research. All had an efficacy over 50% against symptomatic disease: NVX‐CoV2373 (∼96%), BNT162b2 (∼95%), mRNA‐1273 (∼94%), Sputnik V (∼92%), AZD1222 (∼81%), BBIBP‐CorV (∼79%), Covaxin (∼78%), Ad26.CoV.S (∼66%) and CoronaVac (∼51%). However, (VE) can be jeopardised rapid emergence spread SARS‐CoV‐2 variants concern (VOCs) that could escape from neutralising antibodies and/or cell‐mediated immunity. Rare adverse events have also been reported soon after administration viral vector mRNA vaccines. Although many vaccines developed, additional effective still needed meet global demand. Promising such as WIBP‐CorV, AD5‐nCOV, ZyCoV‐D, CVnCoV, EpiVacCorona ZF2001 advanced clinical studies. This review describes most relevant mutations spike protein, discusses VE VOCs, presents rare vaccination introduces some promising candidates.

Language: Английский

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Membrane fusion and immune evasion by the spike protein of SARS-CoV-2 Delta variant

Science, Journal Year: 2021, Volume and Issue: 374(6573), P. 1353 - 1360

Published: Oct. 26, 2021

Delta’s spike Understanding the molecular mechanisms of increased transmissibility and immune evasion severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants is critical to guiding current future intervention strategies. Zhang et al . determined cryo–electron microscopy structures full-length protein trimers Delta, Kappa, Gamma SARS-CoV-2 studied their function antigenic properties. The Delta fused membranes more efficiently at low levels cellular receptor ACE2, its pseudotyped viruses infected target cells substantially rapidly than all other tested, possibly least partly accounting for heightened transmissibility. Mutations each variant rearranged surface N-terminal domain but only caused local changes in receptor-binding domain, consistent with greater resistance neutralizing antibodies. These findings elucidate events that have led these adapt human communities evade host immunity. —VV

Language: Английский

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Omicron: What Makes the Latest SARS-CoV-2 Variant of Concern So Concerning?

Journal of Virology, Journal Year: 2022, Volume and Issue: 96(6)

Published: Feb. 28, 2022

Emerging strains of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent disease 2019 (COVID-19) pandemic, that show increased transmission fitness and/or immune evasion are classified as "variants concern" (VOCs). Recently, a SARS-CoV-2 variant first identified in November 2021 South Africa has been recognized fifth VOC, termed "Omicron." What makes this VOC so alarming is high number changes, especially viral Spike protein, and accumulating evidence for efficiency escape from neutralizing antibodies. In an amazingly short time, Omicron outcompeted previously dominating Delta VOC. However, it seems overall less pathogenic than other VOCs. Here, we provide overview mutations genome resulting changes proteins compared to discuss their potential functional consequences.

Language: Английский

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SARS-CoV-2 breakthrough infections elicit potent, broad, and durable neutralizing antibody responses

Cell, Journal Year: 2022, Volume and Issue: 185(5), P. 872 - 880.e3

Published: Jan. 20, 2022

Although infections among vaccinated individuals lead to milder COVID-19 symptoms relative those in unvaccinated subjects, the specificity and durability of antibody responses elicited by breakthrough cases remain unknown. Here, we demonstrate that induce serum-binding -neutralizing are markedly more potent, durable, resilient spike mutations observed variants than subjects who received only 2 doses vaccine. However, show cases, were after infection, three times have serum-neutralizing activity comparable magnitude breadth, indicating an increased number exposures SARS-CoV-2 antigen(s) enhance quality responses. Neutralization SARS-CoV was moderate, however, underscoring importance developing vaccines eliciting broad sarbecovirus immunity for pandemic preparedness.

Language: Английский

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Functional evaluation of the P681H mutation on the proteolytic activation of the SARS-CoV-2 variant B.1.1.7 (Alpha) spike

iScience, Journal Year: 2021, Volume and Issue: 25(1), P. 103589 - 103589

Published: Dec. 10, 2021

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the agent causing COVID-19 pandemic. SARS-CoV-2 B.1.1.7 (Alpha), a WHO variant of concern first identified in United Kingdom late 2020, contains several mutations including P681H spike S1/S2 cleavage site, which predicted to increase by furin, potentially impacting viral cell entry. Here, we studied role mutation We performed assays using fluorogenic peptides mimicking Wuhan-Hu-1 and sequence observed no significant difference furin cleavage. Functional pseudoparticles harboring spikes cell-to-cell fusion demonstrated differences between Wuhan-Hu-1, B.1.1.7, or point mutant. Likewise, growth USA-WA1/2020 isolate culture. Our findings suggest that, although may slightly cleavage, this does not significantly impact entry cell-cell spread.

Language: Английский

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Defining the risk of SARS-CoV-2 variants on immune protection

Nature, Journal Year: 2022, Volume and Issue: 605(7911), P. 640 - 652

Published: March 31, 2022

Language: Английский

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Nucleocapsid mutations in SARS-CoV-2 augment replication and pathogenesis

PLoS Pathogens, Journal Year: 2022, Volume and Issue: 18(6), P. e1010627 - e1010627

Published: June 21, 2022

While SARS-CoV-2 continues to adapt for human infection and transmission, genetic variation outside of the spike gene remains largely unexplored. This study investigates a highly variable region at residues 203-205 in nucleocapsid protein. Recreating mutation found alpha omicron variants an early pandemic (WA-1) background, we find that R203K+G204R is sufficient enhance replication, fitness, pathogenesis SARS-CoV-2. The mutant corresponds with increased viral RNA protein both vitro vivo. Importantly, increases phosphorylation confers resistance inhibition GSK-3 kinase, providing molecular basis virus replication. Notably, analogous alanine substitutions positions 203+204 also increase replication augment phosphorylation, suggesting enhanced through ablation ancestral 'RG' motif. Overall, these results demonstrate variant mutations are key components SARS-CoV-2's continued adaptation infection.

Language: Английский

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