HICC: Humoral Immune Correlates for COVID19: Defining protective responses and critical readouts for Clinical Trials of Vaccines and Therapeutics

HICC：COVID19 的体液免疫相关性：定义疫苗和治疗临床试验的保护性反应和关键读数

• 批准号: MC_PC_20016
• 负责人: Wilhelm Schwaeble
• 金额: $ 101.13万
• 依托单位: University of Cambridge
• 依托单位国家: 英国
• 项目类别: Intramural
• 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=MC_PC_20016
• 关键词: HICC; Humoral; Immune; Correlates; COVID19

SARS-CoV-2 is an emerging virus with very high infectivity and risk of death in those with severe respiratory symptoms. To maximise our success in protecting people against this disease, we urgently need to understand and develop highly accurate tests to identify when a person has developed a protective immune response versus a COVID-19 disease response. We do not understand the antibody response differences between individuals who have mild SARS-CoV-2 infection and high risk patients that progress to life threatening disease. Understanding specific differences will help us develop tests to diagnose the likelihood of severe disease, and vaccines to prevent them. We will use cutting edge, high throughput technologies to identify in detail the functional role of SARS-CoV-2 antibodies in immune protection, their association with disease severity and the duration of immunity after infection. Importantly, we will turn this information into tests which will be used to:1. Identify when NHS-staff have evidence of protective antibody responses to SARS-CoV-2. This is urgently needed to manage NHS staff returns, guide public health and government policy.2. Provide clinical tests to assist the development and evaluation of safe vaccines and therapies for the treatment of the sickest patients.

SARS-CoV-2 是一种新出现的病毒，对患有严重呼吸道症状的人具有极高的传染性和死亡风险。为了最大限度地成功保护人们免受这种疾病的侵害，我们迫切需要了解并开发高度准确的测试，以确定一个人何时产生了保护性免疫反应而不是 COVID-19 疾病反应。我们不了解轻度 SARS-CoV-2 感染者与进展为危及生命疾病的高危患者之间的抗体反应差异。了解具体差异将有助于我们开发测试来诊断严重疾病的可能性，并开发疫苗来预防它们。我们将使用尖端的高通量技术来详细确定 SARS-CoV-2 抗体在免疫保护中的功能作用、它们与疾病严重程度和感染后免疫持续时间的关系。重要的是，我们将把这些信息转化为测试，用于：1。确定 NHS 工作人员何时有针对 SARS-CoV-2 的保护性抗体反应的证据。这是管理 NHS 工作人员返回、指导公共卫生和政府政策所迫切需要的。2。提供临床测试，以协助开发和评估用于治疗病情最严重的患者的安全疫苗和疗法。

项目成果

Analysis of Serological Biomarkers of SARS-CoV-2 Infection in Convalescent Samples From Severe, Moderate and Mild COVID-19 Cases.

• DOI: 10.3389/fimmu.2021.748291
• 发表时间: 2021
• 期刊: Frontiers in immunology
• 影响因子: 7.3
• 作者: Castillo-Olivares J;Wells DA;Ferrari M;Chan ACY;Smith P;Nadesalingam A;Paloniemi M;Carnell GW;Ohlendorf L;Cantoni D;Mayora-Neto M;Palmer P;Tonks P;Temperton NJ;Peterhoff D;Neckermann P;Wagner R;Doffinger R;Kempster S;Otter AD;Semper A;Brooks T;Albecka A;James LC;Page M;Schwaeble W;Baxendale H;Heeney JL
• 通讯作者: Heeney JL

SARS-CoV-2-specific nasal IgA wanes 9 months after hospitalisation with COVID-19 and is not induced by subsequent vaccination.

• DOI: 10.1016/j.ebiom.2022.104402
• 发表时间: 2023-01
• 期刊: EBIOMEDICINE
• 影响因子: 11.1
• 作者: Liew, Felicity;Talwar, Shubha;Cross, Andy;Willett, Brian J.;Scott, Sam;Logan, Nicola;Siggins, Matthew K.;Swieboda, Dawid;Sidhu, Jasmin K.;Efstathiou, Claudia;Moore, Shona C.;Davis, Chris;Mohamed, Noura;Nunag, Jose;King, Clara;Thompson, A. A. Roger;Rowland-Jones, Sarah L.;Docherty, Annemarie B.;Chalmers, James D.;Ho, Ling-Pei;Horsley, Alexander;Raman, Betty;Poinasamy, Krisnah;Marks, Michael;Kon, Onn Min;Howard, Luke;Wootton, Daniel G.;Dunachie, Susanna;Quint, Jennifer K.;Evans, Rachael A.;V. Wain, Louise;Fontanella, Sara;Silva, Thushan I. de;Ho, Antonia;Harrison, Ewen;Baillie, J. Kenneth;Semple, Malcolm G.;Brightling, Christopher;Thwaites, Ryan S.;Turtle, Lance;Openshaw, Peter J. M.
• 通讯作者: Openshaw, Peter J. M.

Inhibition of the lectin pathway of complement ameliorates hypocomplementemia and restores serum bactericidal activity in patients with severe COVID-19.

• DOI: 10.1002/ctm2.980
• 发表时间: 2022-07
• 期刊: Clinical and translational medicine
• 影响因子: 10.6

Breadth of neutralizing antibody responses to SARS-CoV-2 variants of concern is augmented by vaccination following prior infection; studies in UK healthcare workers and immunodeficient patients

通过在先前感染后接种疫苗，可以增强对所关注的 SARS-CoV-2 变体的中和抗体反应的广度；

• DOI: 10.6084/m9.figshare.14740371
• 发表时间: 2021
• 作者: Nadesalingam A

Secondary Complement Deficiency Impairs Anti-Microbial Immunity to Klebsiella pneumoniae and Staphylococcus aureus During Severe Acute COVID-19.

• DOI: 10.3389/fimmu.2022.841759
• 发表时间: 2022
• 期刊: Frontiers in immunology
• 影响因子: 7.3