The G2P2 virology consortium: keeping pace with SARS-CoV-2 variants, providing evidence to vaccine policy, and building agility for the next pandemic

G2P2 病毒学联盟:跟上 SARS-CoV-2 变种的步伐,为疫苗政策提供证据,并为下一次大流行建立敏捷性

基本信息

  • 批准号:
    MR/Y004205/1
  • 负责人:
  • 金额:
    $ 993.04万
  • 依托单位:
  • 依托单位国家:
    英国
  • 项目类别:
    Research Grant
  • 财政年份:
    2023
  • 资助国家:
    英国
  • 起止时间:
    2023 至 无数据
  • 项目状态:
    未结题

项目摘要

Since arising in China from a single zoonotic event in 2019, SARS-CoV-2 variants of concern (VOCs) have evolved through mutation and selection with Alpha, Delta, and Omicron becoming sequentially dominant worldwide, contrasting with other VOCs that have been regionally dominant e.g., Beta in South Africa and Gamma in South America. VOCs have evolved independently from the early virus (Wuhan), rather than sequentially from one to another, potentially implying differing pathways to dominance as each VOC has been replaced by a "fitter" VOC to drive new waves of infection. This pattern of evolution can be explained by immune escape combining with adaptive changes to the human host to confer more efficient replication and transmission in humans. The deployment of effective vaccines has significantly reduced COVID19 associated hospitalisation, morbidity and mortality, yet high infection rates persist even in vaccinated/infected populations thus providing the opportunity for further viral evolution and the genesis of novel VOCs. Indeed, what is being observed with SARS-CoV-2 is consistent with previous work in other seasonal respiratory infections, showing that immune responses reduce symptoms from a second infection but are less effective at suppressing re-infection and inhibiting onward transmission.The Omicron VOC represents the first substantial antigenic shift, with >30 mutations in Spike rendering the virus markedly less sensitive to neutralisation by antibodies induced by vaccination and/or prior infection. Importantly, Spike adaptation to escape human immunity was linked to increased replication in vitro and in vivo, and reduced pathogenicity in humans as well as animal models (though immune memory also presumably contributes to reduced Omicron pathogenicity in humans). Since the emergence of the first Omicron isolate, BA.1, further Omicron subvariants have evolved, yielding a series of sub-lineages, BA.1-5, and now BQ.1.1 and XBB, that co-circulate and recombine thus acquiring additional adaptive mutations. These mutations have enhanced replication, transmission and escape from the host adaptive and innate immunity. In sum, the ongoing sequence diversification and evolution of SARS-CoV-2 as it transitions to endemicity, together with the inevitable waning of adaptive immunity at the level of individuals and populations, raise the very real possibility that the pathogenicity and transmissibility of future VOCs may increase, thus increasing disease burden and intensifying the pressures on health systems globally. Indeed, as of Jan 2023, there were over 11,000 hospitalisations due to COVID19. In preparing for the emergence of a new VOC, our consortium will work collaboratively to: 1) rapidly risk-assess new variants as they arise for increased transmission and pathogenesis; and 2) define and mechanistically dissect the viral sequence signatures/ patterns that are carried by VOCs and that underpin phenotypic changes. These data will help provide early warning as constellations of mutations of concern arise, and inform the scientific and public health responses to novel VOCs, providing scientific evidence to policy aimed to for example intensify vaccination programmes and/or refine the vaccines themselves.
自2019年在中国发生单一人畜共患病事件以来,SARS-CoV-2变异体(VOC)通过突变和选择而演变,Alpha,Delta和Omicron在全球范围内依次占主导地位,与其他区域占主导地位的VOC形成对比,例如,Beta在南非,Gamma在南美洲。VOC从早期病毒(武汉)独立进化,而不是从一种到另一种依次进化,这可能意味着不同的主导途径,因为每种VOC都被“更适合”的VOC取代,以推动新的感染浪潮。这种进化模式可以解释为免疫逃逸与人类宿主的适应性变化相结合,以赋予人类更有效的复制和传播。有效疫苗的部署显著降低了COVID 19相关的住院、发病率和死亡率,但即使在接种疫苗/感染人群中,高感染率也持续存在,从而为病毒进一步进化和新型VOC的产生提供了机会。事实上,SARS-CoV-2的观察结果与之前在其他季节性呼吸道感染中的研究结果一致,表明免疫反应减轻了第二次感染的症状,但在抑制再次感染和抑制向前传播方面效果较差。Omicron VOC代表了第一个实质性的抗原转变,刺突中>30个突变使得病毒对由疫苗接种和/或先前感染诱导的抗体的中和作用明显不敏感。重要的是,逃避人类免疫的刺突适应与体外和体内复制增加以及人类和动物模型中致病性降低有关(尽管免疫记忆也可能有助于降低人类中的Omicron致病性)。自从第一个Omicron分离株BA.1出现以来,进一步的Omicron亚变体已经进化,产生了一系列的亚谱系BA.1-5,现在是BQ.1.1和XBB,它们共同循环和重组,从而获得额外的适应性突变。这些突变增强了复制、传播和逃避宿主的适应性和先天性免疫。总而言之,SARS-CoV-2在向地方性转变过程中的序列多样化和进化,以及个人和群体水平上的适应性免疫力不可避免的减弱,增加了未来VOC的致病性和传播性可能增加的真实的可能性,从而增加了疾病负担并加剧了全球卫生系统的压力。事实上,截至2023年1月,因COVID 19而住院的人数超过11,000人。在为新VOC的出现做准备时,我们的联盟将合作开展以下工作:1)快速评估新变体的风险,因为它们会增加传播和发病机制; 2)定义并机械地剖析VOC携带的病毒序列特征/模式,并支持表型变化。这些数据将有助于在出现令人担忧的突变时提供早期预警,并为科学和公共卫生应对新的VOC提供信息,为旨在加强疫苗接种计划和/或改进疫苗本身的政策提供科学证据。

项目成果

期刊论文数量(0)
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Wendy Barclay其他文献

GGCX promotes Eurasian avian-like H1N1 swine influenza virus adaption to interspecies receptor binding
GGCX 促进欧亚类鸟 H1N1 猪流感病毒适应种间受体结合
  • DOI:
    10.1038/s41467-025-55903-0
  • 发表时间:
    2025-01-15
  • 期刊:
  • 影响因子:
    15.700
  • 作者:
    Jiahui Zou;Meijun Jiang;Rong Xiao;Huimin Sun;Hailong Liu;Thomas Peacock;Shaoyu Tu;Tong Chen;Jinli Guo;Yaxin Zhao;Wendy Barclay;Shengsong Xie;Hongbo Zhou
  • 通讯作者:
    Hongbo Zhou
SARS-CoV-2 human challenge reveals biomarkers that discriminate early and late phases of respiratory viral infections
SARS-CoV-2 人体挑战揭示了可区分呼吸道病毒感染早期和晚期阶段的生物标志物
  • DOI:
    10.1038/s41467-024-54764-3
  • 发表时间:
    2024-11-30
  • 期刊:
  • 影响因子:
    15.700
  • 作者:
    Joshua Rosenheim;Rishi K. Gupta;Clare Thakker;Tiffeney Mann;Lucy C. K. Bell;Claire M. Broderick;Kieran Madon;Loukas Papargyris;Pete Dayananda;Andrew J. Kwok;James Greenan-Barrett;Helen R. Wagstaffe;Emily Conibear;Joe Fenn;Seran Hakki;Rik G. H. Lindeboom;Lisa M. Dratva;Briac Lemetais;Caroline M. Weight;Cristina Venturini;Myrsini Kaforou;Michael Levin;Mariya Kalinova;Alex J. Mann;Andrew Catchpole;Julian C. Knight;Marko Z. Nikolić;Sarah A. Teichmann;Ben Killingley;Wendy Barclay;Benjamin M. Chain;Ajit Lalvani;Robert S. Heyderman;Christopher Chiu;Mahdad Noursadeghi
  • 通讯作者:
    Mahdad Noursadeghi

Wendy Barclay的其他文献

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{{ truncateString('Wendy Barclay', 18)}}的其他基金

Flu: TrailMap-One Health
流感:TrailMap-One Health
  • 批准号:
    MR/Y03368X/1
  • 财政年份:
    2024
  • 资助金额:
    $ 993.04万
  • 项目类别:
    Research Grant
Flu:Trailmap
流感:路线图
  • 批准号:
    BB/Y007093/1
  • 财政年份:
    2023
  • 资助金额:
    $ 993.04万
  • 项目类别:
    Research Grant
Flu-MAP
流感MAP
  • 批准号:
    BB/X006204/1
  • 财政年份:
    2022
  • 资助金额:
    $ 993.04万
  • 项目类别:
    Research Grant
G2P-UK; A National Virology Consortium to address phenotypic consequences of SARSCoV-2 genomic variation
G2P-英国;
  • 批准号:
    MR/W005611/1
  • 财政年份:
    2021
  • 资助金额:
    $ 993.04万
  • 项目类别:
    Research Grant
Investigating the role of ANP32A in the replication of Avian influenza Virus
研究 ANP32A 在禽流感病毒复制中的作用
  • 批准号:
    BB/S008292/1
  • 财政年份:
    2019
  • 资助金额:
    $ 993.04万
  • 项目类别:
    Research Grant
Discovery and characterization of swine host factors required to support swine influenza virus replication.
支持猪流感病毒复制所需的猪宿主因子的发现和表征。
  • 批准号:
    BB/R013071/1
  • 财政年份:
    2018
  • 资助金额:
    $ 993.04万
  • 项目类别:
    Research Grant
Developing an in vitro approach to study transmission of respiratory viruses.
开发一种体外方法来研究呼吸道病毒的传播。
  • 批准号:
    NC/K00042X/1
  • 财政年份:
    2013
  • 资助金额:
    $ 993.04万
  • 项目类别:
    Research Grant
Highly differentiated cultures of ferret airway epithelium for the study of respiratory viruses, including influenza.
雪貂气道上皮的高度分化培养物,用于研究呼吸道病毒(包括流感)。
  • 批准号:
    G1000033/1
  • 财政年份:
    2011
  • 资助金额:
    $ 993.04万
  • 项目类别:
    Research Grant
The role of the novel influenza A protein PB1-F2 in viral pathogenesis in the avian species
新型甲型流感蛋白 PB1-F2 在禽类病毒发病机制中的作用
  • 批准号:
    BB/C516495/2
  • 财政年份:
    2007
  • 资助金额:
    $ 993.04万
  • 项目类别:
    Research Grant
Identification of cellular genes that affect host range restriction of influenza virus
影响流感病毒宿主范围限制的细胞基因的鉴定
  • 批准号:
    G0600006/1
  • 财政年份:
    2007
  • 资助金额:
    $ 993.04万
  • 项目类别:
    Research Grant

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RADx-Rad Discoveries & Data: Consortium Coordination Center Program Organization
RADx-Rad 发现
  • 批准号:
    10745886
  • 财政年份:
    2023
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    $ 993.04万
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Texas NeuroAIDS Research Center
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Viral Immunity and VAccination (VIVA) Human Immunology Project Consortium (HIPC)
病毒免疫和疫苗接种 (VIVA) 人类免疫学项目联盟 (HIPC)
  • 批准号:
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CHARTER Plus: A resource for cutting-edge research on neurological function and mental health in people with HIV and substance use disorders across the lifespan
CHARTER Plus:艾滋病毒感染者和药物使用障碍患者整个生命周期神经功能和心理健康的前沿研究资源
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    $ 993.04万
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Viral Immunity and VAccination (VIVA) Human Immunology Project Consortium (HIPC)
病毒免疫和疫苗接种 (VIVA) 人类免疫学项目联盟 (HIPC)
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慢性艾滋病毒感染和可卡因自我给药期间的单细胞转录组和表观基因组变化
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    10629335
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    2022
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    $ 993.04万
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Single cell transcriptomic and epigenomic changes during chronic HIV infection and cocaine self-administration
慢性艾滋病毒感染和可卡因自我给药期间的单细胞转录组和表观基因组变化
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  • 批准号:
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