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是一种新兴的病毒，患有严重呼吸道症状的病毒具有很高的感染性和死亡风险。为了最大程度地利用我们保护人们免受这种疾病的影响，我们迫切需要理解和开发高度准确的测试，以确定何时与Covid-19疾病反应相比，一个人何时发展了保护性免疫反应。我们不了解患有轻度SARS-COV-2感染的个体与高风险患者的抗体反应差异，这些患者发展为威胁生命的疾病。了解具体的差异将有助于我们开发测试以诊断严重疾病的可能性，以及防止它们的疫苗。我们将使用最先进的高吞吐量技术详细识别SARS-COV-2抗体在免疫保护，其与疾病严重程度的关联以及感染后免疫持续时间的关系。重要的是，我们将将这些信息转变为用于以下方式的测试：1。确定何时NHS-STAFF具有对SARS-COV-2的保护性抗体反应的证据。迫切需要这样做才能管理NHS员工返回，指导公共卫生和政府政策2。提供临床测试，以帮助开发和评估安全疫苗和治疗最病患者的疗法。

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