A UK underpinning platform to study immunology and immunopathology of COVID-19:The UK Coronavirus Immunology Consortium

英国研究 COVID-19 免疫学和免疫病理学的基础平台：英国冠状病毒免疫学联盟

• 批准号: MR/V028448/1
• 负责人: Paul Moss
• 金额: $ 838万
• 依托单位: University of Birmingham
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2020
• 资助国家: 英国
• 起止时间: 2020 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FV028448%2F1
• 关键词: UK; underpinning; platform; study; immunology

The immune response to SARS-CoV-2 infection is the critical determinant of clinical outcome for patients but although this can suppress virus replication (immunity) it can also cause damage to tissues such as the lung (immunopathology). It is unclear how effective immunity is established or why it damages tissues. Many UK research groups have initiated research and UK-CIC will bring together a consortium of 17 UK centres to coordinate coronavirus immunology research.We will work on 5 questions:-the features of immunity during initial infection and how this relates to clinical outcome of individual patients. SARS-CoV-2 infection triggers an immediate (innate: interferon and white cell) and delayed (adaptive: antibody and cellular) immune response. How these develop and interact is currently unclear but will determine how quickly the infection is cleared. We will study this in patients with mild and severe infection. A number of risk factors for severe Covid-19 infection have been identified including age, gender, obesity and ethnicity. These will be studied in relation to the features of the initial immune response.-how effective immunity is established and maintained to prevent re-infectionAfter infection the immune response develops some 'memory' of the infection and this helps to prevent reinfection. For some infections (e.g. measles) this protection is virtually complete; for others (such as the common cold) this protection is brief. We do not know what the situation will be for SARS-CoV-2. This work will take samples from people in the first year after infection and measure the virus-specific immune response. We will examine the fine details of how the immune system kills the virus and the longevity of this response. We will examine a broad representation of population groups to do this work effectively and compare groups of different ages and backgrounds.-the mechanisms by which the immune system can damage tissue and how this can be stoppedIn severe or fatal infection the problems arise due to two mechanisms:(1) The virus infects and damages tissue(2) The immune response to the virus can itself damage tissueIn this research theme we will investigate the relative importance of these two problems and try to find ways to prevent them. This will involve taking blood and tissue samples from patients with severe disease and also using post mortem tissue.-if immunity to mild 'seasonal' coronaviruses alters the outcome of SARS-CoV-2 infection The term coronavirus was first used in 1965 to describe identification of a common cold virus and these viruses circulate widely in the community. It is thought that the immune response to these viruses may potentially 'cross-react' with the new SARS-CoV-2 coronavirus, perhaps giving some people relative protection against infection. We will investigate this possibility and assess how it might happen. Here we will use blood samples in the laboratory to assess their recognition of both viruses and also see if blood samples frozen down before the Covid-19 pandemic make any response to the new virus. -the details by which the virus 'evades' the immune system and how this could be targeted by new treatments.Viruses can only grow, spread and cause disease if they are able to evade being killed by the immune system. If we can understand how this happens we might be able to develop new drugs that can block this response and allow the virus to take control and eliminate the virus. This work takes place in the laboratory using viral infection studies of cells. UK-CIC will work with other major recent UK investments in Covid-19 biology and represents an essential additional pillar of UK research infrastructure to hasten the control of the pandemic.

对SARS-CoV-2感染的免疫反应是患者临床结果的关键决定因素，但尽管这可以抑制病毒复制（免疫），但也可能导致肺等组织损伤（免疫病理学）。目前还不清楚有效的免疫力是如何建立的，也不清楚它为什么会损害组织。许多英国研究小组已经开始研究，UK-CIC将召集17个英国中心的联盟来协调冠状病毒免疫学研究。我们将研究5个问题：-初次感染期间的免疫特征以及这与个体患者临床结果的关系。SARS-CoV-2感染触发即时（先天性：干扰素和白色细胞）和延迟（适应性：抗体和细胞）免疫应答。目前尚不清楚这些疾病是如何发展和相互作用的，但将决定感染被清除的速度。我们将在轻度和重度感染患者中研究这一点。已经确定了一些严重的Covid-19感染的风险因素，包括年龄，性别，肥胖和种族。这些将与初始免疫反应的特征相关进行研究。如何建立和维持有效的免疫力以防止再感染后，免疫反应会产生一些感染的“记忆”，这有助于防止再感染。对于某些传染病（如麻疹），这种保护几乎是完全的;对于其他传染病（如普通感冒），这种保护是短暂的。我们不知道SARS-CoV-2的情况会如何。这项工作将在感染后的第一年从人们身上采集样本，并测量病毒特异性免疫反应。我们将研究免疫系统如何杀死病毒的细节以及这种反应的持久性。我们将研究人口群体的广泛代表性，以有效地开展这项工作，并比较不同年龄和背景的群体。在严重或致命的感染中，由于两种机制引起的问题：（1）病毒感染和破坏组织（2）对病毒的免疫反应本身可以破坏组织在本研究主题中，我们将研究这两个问题的相对重要性，并试图找到预防它们的方法。这将涉及从患有严重疾病的患者身上采集血液和组织样本，并使用死后组织。对温和的“季节性”冠状病毒的免疫是否会改变SARS-CoV-2感染的结果冠状病毒一词首次使用于1965年，用于描述普通感冒病毒的鉴定，这些病毒在社区中广泛传播。人们认为，对这些病毒的免疫反应可能会与新的SARS-CoV-2冠状病毒发生潜在的“交叉反应”，也许会给一些人相对的保护。我们将研究这种可能性，并评估它是如何发生的。在这里，我们将使用实验室中的血液样本来评估他们对这两种病毒的识别，并观察在新冠肺炎大流行之前冻结的血液样本是否对新病毒产生任何反应。- 病毒如何“逃避"免疫系统的细节，以及新的治疗方法如何针对这一点。病毒只有在能够逃避免疫系统的杀死时才能生长、传播和引起疾病。如果我们能够理解这种情况是如何发生的，我们可能能够开发出新的药物，可以阻止这种反应，并允许病毒控制和消除病毒。这项工作是在实验室进行的，使用细胞的病毒感染研究。UK-CIC将与英国近期在Covid-19生物学领域的其他主要投资合作，并代表英国研究基础设施的一个重要额外支柱，以加快对大流行病的控制。

项目成果

Structural definition of HLA class II-presented SARS-CoV-2 epitopes reveals a mechanism to escape pre-existing CD4+ T cell immunity

• DOI: 10.1016/j.celrep.2023.112827
• 发表时间: 2023-07
• 期刊: Cell Reports
• 影响因子: 8.8
• 作者: Yuan Chen;Georgina H Mason;D. O. Scourfield;Alexander Greenshields-Watson;T. Haigh;A. Sewell;H. Long;A. Gallimore;P. Rizkallah;B. MacLachlan;A. Godkin

T-cell and antibody responses to first BNT162b2 vaccine dose in previously infected and SARS-CoV-2-naive UK health-care workers: a multicentre prospective cohort study.

• DOI: 10.1016/s2666-5247(21)00275-5
• 发表时间: 2022-01
• 期刊: The Lancet. Microbe
• 作者: Angyal A;Longet S;Moore SC;Payne RP;Harding A;Tipton T;Rongkard P;Ali M;Hering LM;Meardon N;Austin J;Brown R;Skelly D;Gillson N;Dobson SL;Cross A;Sandhar G;Kilby JA;Tyerman JK;Nicols AR;Spegarova JS;Mehta H;Hornsby H;Whitham R;Conlon CP;Jeffery K;Goulder P;Frater J;Dold C;Pace M;Ogbe A;Brown H;Ansari MA;Adland E;Brown A;Chand M;Shields A;Matthews PC;Hopkins S;Hall V;James W;Rowland-Jones SL;Klenerman P;Dunachie S;Richter A;Duncan CJA;Barnes E;Carroll M;Turtle L;de Silva TI;PITCH Consortium
• 通讯作者: PITCH Consortium

IFITM3 restricts virus-induced inflammatory cytokine production by limiting Nogo-B mediated TLR responses.

• DOI: 10.1038/s41467-022-32587-4
• 发表时间: 2022-09-08
• 期刊: Nature communications
• 影响因子: 16.6

Treatment of COVID-19 with remdesivir in the absence of humoral immunity: a case report.

• DOI: 10.1038/s41467-020-19761-2
• 发表时间: 2020-12-14
• 期刊: Nature communications
• 影响因子: 16.6
• 作者: Buckland MS;Galloway JB;Fhogartaigh CN;Meredith L;Provine NM;Bloor S;Ogbe A;Zelek WM;Smielewska A;Yakovleva A;Mann T;Bergamaschi L;Turner L;Mescia F;Toonen EJM;Hackstein CP;Akther HD;Vieira VA;Ceron-Gutierrez L;Periselneris J;Kiani-Alikhan S;Grigoriadou S;Vaghela D;Lear SE;Török ME;Hamilton WL;Stockton J;Quick J;Nelson P;Hunter M;Coulter TI;Devlin L;CITIID-NIHR COVID-19 BioResource Collaboration;MRC-Toxicology Unit COVID-19 Consortium;Bradley JR;Smith KGC;Ouwehand WH;Estcourt L;Harvala H;Roberts DJ;Wilkinson IB;Screaton N;Loman N;Doffinger R;Lyons PA;Morgan BP;Goodfellow IG;Klenerman P;Lehner PJ;Matheson NJ;Thaventhiran JED
• 通讯作者: Thaventhiran JED