PITCH2 - Protective Immunity through T Cells in Healthcare workers 2

PITCH2 - 通过医护人员的 T 细胞实现保护性免疫 2

• 批准号: MR/X009297/1
• 负责人: Susanna Dunachie
• 金额: $ 257.86万
• 依托单位: University of Oxford
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2023
• 资助国家: 英国
• 起止时间: 2023 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FX009297%2F1
• 关键词: PITCH2; Protective; Immunity; through; Cells

COVID-19 has had a devastating impact on lives for many reasons, including illness, loss of life, restrictions to way of life and economic losses. We now see lower rates of severe disease and death despite continued infections from the virus (severe acute respiratory syndrome coronavirus 2: SARS-CoV-2), but we need to protect people with immune problems and be ready for future variants and related viruses. It is crucial that we understand how people's immune systems protect against both infection and severe disease, and how long immunity lasts. This information tells us whether we need to give booster vaccines again, who is at increased risk of infection and severe disease, how to fine tune the next generation of vaccines and can guide development of new drug treatments. Much research on the immune response to COVID-19 focusses on measuring antibodies in the blood, but there is a second vital arm to the body's learned response to infection: T cells. T cells are a group of white blood cells patrolling the bloodstream to defend against infection, and can be trained by vaccination and/or previous infection to recognise and destroy the virus causing COVID-19. T cells are likely to be particularly important at preventing severe disease, but are difficult to measure because fresh blood samples and specialised skills and equipment required. We have established a national group to track the T cell response to the SARS-CoV-2 virus in over time in over 2000 healthcare workers working in one of five cities (Birmingham, Liverpool, Newcastle, Oxford and Sheffield). This group, called the PITCH (Protective Immunity through T Cells in Healthcare workers) consortium, includes researchers from UK Health Security Agency who run the wider SIREN study which undertakes regular PCR screening and antibody testing from 44,546 healthcare workers in 135 NHS sites across the UK. PITCH allows study of the immune response in greater detail in our subgroup. So far our research findings have helped the UK government make decisions about when to give vaccines and who remains especially vulnerable. We demonstrated that people with previous infection make a much better antibody and T cell response after receiving vaccines, even after the third (booster) dose. We also showed that a longer dosing interval for the Pfizer vaccine gave higher antibody responses and lower but better memory quality T cell responses than a short dosing interval. Our latest work shows that after two doses of vaccine, the antibody response declines over six months, but the T cell response is well maintained, re-enforcing the idea that T cells are important for long term protection. T cells in vaccinated people still work well against the Omicron variant, which evades much of the body's neutralising antibody response. We have shared our T cell laboratory techniques with other researchers, and we work with national study teams such as OCTAVE to look at T cell responses in patients with immune issues compared to our healthier population of healthcare workers. We are now applying for funding to maintain the systems we have set up for the PITCH consortium. We need to follow-up our group of healthcare workers to see if the antibody and T cell response is wearing off in time, and to measure how people's immune response deal with any future variants of the virus. We also have an opportunity to learn more about the immune response to influenza (flu) because there has not been any flu in circulation since winter 2019/2020 due to the restrictions put in place for COVID-19. We will work together with the British Society for Immunology to explain our research to healthcare workers and the wider public, and listen to opinions on what the important questions are. We have assembled a highly productive group of researchers and will use PITCH2 as a springboard for long term deeper research studies to answer questions on the character and duration of immunity to SARS-CoV-2 virus and flu.

COVID-19对生活造成了毁灭性的影响，原因有很多，包括疾病、生命损失、生活方式的限制和经济损失。我们现在看到，尽管病毒（严重急性呼吸道综合征冠状病毒2：SARS-CoV-2）持续感染，但严重疾病和死亡率较低，但我们需要保护有免疫问题的人，并为未来的变种和相关病毒做好准备。至关重要的是，我们要了解人们的免疫系统如何保护免受感染和严重疾病，以及免疫力持续多久。这些信息告诉我们是否需要再次接种加强疫苗，谁感染和严重疾病的风险增加，如何微调下一代疫苗，并可以指导新药治疗的开发。许多关于COVID-19免疫反应的研究都集中在测量血液中的抗体上，但身体对感染的学习反应还有第二个重要的手臂：T细胞。T细胞是一群在血液中巡逻以抵御感染的白色血细胞，可以通过接种疫苗和/或之前的感染进行训练，以识别和破坏引起COVID-19的病毒。T细胞在预防严重疾病方面可能特别重要，但由于需要新鲜血液样本和专业技能和设备，因此难以测量。我们已经建立了一个全国性的小组，在五个城市（伯明翰、利物浦、纽卡斯尔、牛津和谢菲尔德）之一工作的2000多名医护人员中跟踪T细胞对SARS-CoV-2病毒的反应。该小组被称为PITCH（通过T细胞在医疗工作者中的保护性免疫）联盟，包括来自英国卫生安全局的研究人员，他们进行了更广泛的SIREN研究，该研究对英国135个NHS站点的44，546名医疗工作者进行定期PCR筛查和抗体检测。PITCH允许在我们的亚组中更详细地研究免疫应答。到目前为止，我们的研究结果已经帮助英国政府决定何时接种疫苗以及谁仍然特别脆弱。我们证明，以前感染过的人在接受疫苗后，甚至在第三次（加强）接种后，抗体和T细胞反应都要好得多。我们还表明，辉瑞疫苗较长的给药间隔比短的给药间隔产生更高的抗体应答和更低但更好的记忆质量的T细胞应答。我们的最新研究表明，在接种两剂疫苗后，抗体反应在六个月内下降，但T细胞反应得到了很好的维持，这再次强化了T细胞对长期保护很重要的观点。接种疫苗的人的T细胞仍然可以很好地对抗Omicron变体，这种变体可以逃避身体的中和抗体反应。我们与其他研究人员分享了我们的T细胞实验室技术，并与OCTAVE等国家研究团队合作，研究免疫问题患者的T细胞反应，并与我们健康的医疗保健工作者人群进行比较。我们现在正在申请资金，以维护我们为PITCH财团建立的系统。我们需要对我们的医护人员小组进行随访，看看抗体和T细胞反应是否及时消失，并测量人们的免疫反应如何应对病毒的任何未来变种。我们亦有机会了解更多有关流感（流感）的免疫反应，因为自2019/2020年冬季以来，由于COVID-19实施的限制，没有任何流感流行。我们将与英国免疫学会合作，向医护人员和广大公众解释我们的研究，并听取对重要问题的意见。 我们已经组建了一个高效的研究小组，并将使用PITCH 2作为长期深入研究的跳板，以回答有关SARS-CoV-2病毒和流感免疫力的特征和持续时间的问题。

项目成果

Rapid escape of new SARS-CoV-2 Omicron variants from BA.2-directed antibody responses.

• DOI: 10.1016/j.celrep.2023.112271
• 发表时间: 2023-04-25
• 期刊: Cell reports
• 影响因子: 8.8

Booster Vaccination Against SARS-CoV-2 Induces Potent Immune Responses in People With Human Immunodeficiency Virus.

• DOI: 10.1093/cid/ciac796
• 发表时间: 2023-01-13
• 期刊: Clinical infectious diseases : an official publication of the Infectious Diseases Society of America

Obesity Differs from Diabetes Mellitus in Antibody and T Cell Responses Post COVID-19 Recovery

• DOI: 10.1101/2023.06.14.23291375
• 发表时间: 2023-06
• 期刊: Clinical and experimental immunology
• 影响因子: 4.6
• 作者: M. Ali;S. Longet;I. Neale;P. Rongkard;F. Chowdhury;J. Hill;A. Brown;S. Laidlaw;T. Tipton

Age- and sex-specific differences in immune responses to BNT162b2 COVID-19 and live-attenuated influenza vaccines in UK adolescents

英国青少年对 BNT162b2 COVID-19 和减毒流感疫苗的免疫反应存在年龄和性别差异

• DOI: 10.1101/2023.07.24.23293091
• 发表时间: 2023
• 作者: Jay C

A delicate balance between antibody evasion and ACE2 affinity for Omicron BA.2.75.

• DOI: 10.1016/j.celrep.2022.111903
• 发表时间: 2023-01-31
• 期刊: Cell reports
• 影响因子: 8.8