The Role Of Antibody in Enabling Cell-mediated Control of HCMV Infection

抗体在细胞介导的 HCMV 感染控制中的作用

• 批准号: MR/S00971X/1
• 负责人: Richard Stanton
• 金额: $ 77.73万
• 依托单位: CARDIFF UNIVERSITY
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2019
• 资助国家: 英国
• 起止时间: 2019 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FS00971X%2F1
• 关键词: Role; Antibody; Enabling; Cell; mediated

Human cytomegalovirus (HCMV) is a serious clinical problem. If a mother catches it during pregnancy and it passes to the foetus, the foetus may die, or it may suffer from lifelong disabilities including deafness, blindness or intellectual disability. In the UK over 5,000 babies contract CMV every year, while in America, over 44,000 babies will catch it. It also causes major problems in patients with weakened immune systems, such as transplant recipients or HIV sufferers. The virus is a major cause of suffering, and places a high financial burden on the health system; caring for a single CMV infected baby costs >$330,000 per year. Current treatment are antivirals, however these can be very toxic, and the virus can rapidly become resistant to the drugs. For many viruses, and in the study of cancer, great success has been achieved by giving patients antibodies that can bind to cells, and activate immune cells to kill infected or cancerous cells. HCMV antibodies can control infection in a similar way, yet we have very little understanding of which HCMV proteins these antibodies are binding, or which immune cells are responsible for killing the infected cells. Answering these questions is important to generating optimal vaccines, novel therapies, and for understanding how the immune system controls disease in patients.We have identified all the HCMV proteins that are present on the surface of infected cells, and shown that antibodies can bind to these proteins, enabling them to be 'seen' by immune cells. We will now exploit these observations to determine which virus proteins are best at activating immune cells, and which immune cells are best at controlling the infection. We will also investigate the ways that the virus might try and prevent antibodies from binding to infected cells, so that we can circumvent these 'evasion' mechanisms. Taken together, this data will enable us to design effective antibodies that are optimised for controlling HCMV disease in human patients, and will enable the rational design of more effective vaccine strategies.

人类巨细胞病毒（HCMV）是一个严重的临床问题。如果母亲在怀孕期间感染该病毒并传染给胎儿，胎儿可能会死亡，或者可能遭受终身残疾，包括耳聋、失明或智力障碍。在英国，每年有超过 5,000 名婴儿感染巨细胞病毒，而在美国，超过 44,000 名婴儿会感染 CMV。它还会给免疫系统较弱的患者（例如移植受者或艾滋病毒患者）带来严重问题。该病毒是造成痛苦的主要原因，给卫生系统带来沉重的经济负担；照顾一个感染 CMV 的婴儿每年的费用超过 330,000 美元。目前的治疗方法是抗病毒药物，但它们的毒性可能很大，而且病毒会很快对药物产生耐药性。对于许多病毒以及癌症研究来说，通过向患者提供可以与细胞结合并激活免疫细胞杀死感染细胞或癌细胞的抗体已经取得了巨大成功。 HCMV 抗体可以以类似的方式控制感染，但我们对这些抗体结合哪些 HCMV 蛋白，或者哪些免疫细胞负责杀死受感染的细胞知之甚少。回答这些问题对于产生最佳疫苗、新疗法以及了解免疫系统如何控制患者疾病非常重要。我们已经鉴定了受感染细胞表面存在的所有 HCMV 蛋白，并表明抗体可以与这些蛋白结合蛋白质，使它们能够被免疫细胞“看到”。我们现在将利用这些观察结果来确定哪些病毒蛋白最能激活免疫细胞，以及哪些免疫细胞最能控制感染。我们还将研究病毒可能尝试阻止抗体与受感染细胞结合的方式，以便我们可以规避这些“逃避”机制。总而言之，这些数据将使我们能够设计出有效的抗体，优化控制人类患者的 HCMV 疾病，并使我们能够合理设计更有效的疫苗策略。

项目成果

Suppression of MR1 by human cytomegalovirus inhibits MAIT cell activation.

• DOI: 10.3389/fimmu.2023.1107497
• 发表时间: 2023
• 期刊: FRONTIERS IN IMMUNOLOGY
• 影响因子: 7.3
• 作者: Ashley, Caroline L.;McSharry, Brian P.;McWilliam, Hamish E. G.;Stanton, Richard J.;Fielding, Ceri A.;Mathias, Rommel A.;Fairlie, David P.;McCluskey, James;Villadangos, Jose A.;Rossjohn, Jamie;Abendroth, Allison;Slobedman, Barry
• 通讯作者: Slobedman, Barry

Evaluating the antimicrobial efficacy of long-lasting hand sanitizers on skin.

评估长效洗手液对皮肤的抗菌功效。

• DOI: 10.1016/j.jhin.2023.08.020
• 发表时间: 2023
• 期刊: The Journal of hospital infection
• 作者: Duggan K

Quantitative proteomic analysis of SARS-CoV-2 infection of primary human airway ciliated cells and lung epithelial cells demonstrates the effectiveness of SARS-CoV-2 innate immune evasion.

• DOI: 10.12688/wellcomeopenres.17946.1
• 发表时间: 2022
• 期刊: Wellcome open research

Peptide Derivatives of Platelet-Derived Growth Factor Receptor Alpha Inhibit Cell-Associated Spread of Human Cytomegalovirus

血小板衍生生长因子受体α的肽衍生物抑制人巨细胞病毒的细胞相关传播

• DOI: 10.18725/oparu-39714
• 发表时间: 2021
• 作者: Braun B

Improved control of SARS-CoV-2 by treatment with a nucleocapsid-specific monoclonal antibody.

• DOI: 10.1172/jci162282
• 发表时间: 2022-12-01
• 期刊: JOURNAL OF CLINICAL INVESTIGATION
• 影响因子: 15.9
• 作者: Dangi, Tanushree;Sanchez, Sarah;Class, Jacob;Richner, Michelle;Visvabharathy, Lavanya;Chung, Young Rock;Bentley, Kirsten;Stanton, Richard J.;Koralnik, Igor J.;Richner, Justin M.;Penaloza-MacMaster, Pablo
• 通讯作者: Penaloza-MacMaster, Pablo