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抓住了它，并传递给胎儿，胎儿可能会死亡，或者可能遭受终身残疾，包括耳聋，失明或智力残疾。在英国，每年有超过5,000名婴儿合同CMV，而在美国，超过44,000名婴儿将抓住它。这也会导致免疫系统疲软的患者（例如移植受者或HIV患者）引起重大问题。该病毒是造成苦难的主要原因，并给卫生系统带来了巨大的财务负担。照顾单一CMV感染的婴儿每年费用> 330,000美元。当前的治疗是抗病毒药，但是这些可能是非常毒性的，并且该病毒可以迅速对药物具有抗药性。对于许多病毒，在癌症的研究中，通过给予可以与细胞结合的抗体并激活免疫细胞以杀死感染或癌细胞的抗体取得了巨大成功。 HCMV抗体可以以类似的方式控制感染，但是我们对这些抗体具有结合的HCMV蛋白几乎没有理解，或者免疫细胞负责杀死感染细胞。回答这些问题对于产生最佳疫苗，新型疗法以及了解免疫系统如何控制患者的疾病很重要。我们已经鉴定出存在于感染细胞表面上的所有HCMV蛋白，并表明抗体可以与这些蛋白质结合，从而使它们被免疫细胞“看到”。现在，我们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，哪些免疫细胞最能控制感染。我们还将研究病毒可能试图防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。综上所述，这些数据将使我们能够设计用于控制人类患者HCMV疾病的有效抗体，并能够合理地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