PITCH2 - Protective Immunity through T Cells in Healthcare workers 2

新冠肺炎因多种原因对人们的生活产生了毁灭性的影响，包括疾病、生命损失、生活方式的限制和经济损失。尽管病毒(严重急性呼吸综合征冠状病毒2：SARS-CoV-2)持续感染，但我们现在看到严重疾病和死亡率较低，但我们需要保护有免疫问题的人，并为未来的变异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防御感染和严重疾病，以及免疫持续多长时间。这些信息告诉我们，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。许多关于新冠肺炎免疫反应的研究都集中在测量血液中的抗体上，但人体对感染的获得性反应还有第二个至关重要的手臂：T细胞。T细胞是一组在血液中巡逻以抵御感染的白细胞，可以通过接种疫苗和/或先前的感染来训练，以识别和摧毁导致新冠肺炎的病毒。T细胞在预防严重疾病方面可能特别重要，但很难测量，因为需要新鲜的血液样本和专门的技能和设备。我们已经建立了一个全国性的小组，跟踪在五个城市(伯明翰、利物浦、纽卡斯尔、牛津和谢菲尔德)工作的2000多名医护人员在一段时间内对SARS-CoV-2病毒的T细胞反应。这个被称为Pitch(通过T细胞在医疗保健工作者中的保护免疫)联盟的组织，包括来自英国健康安全局的研究人员，他们进行了更广泛的SIREN研究，对英国135个NHS站点的44,546名医护人员进行了定期的PCR筛查和抗体测试。Pitch可以在我们的亚群中更详细地研究免疫反应。到目前为止，我们的研究结果帮助英国政府做出了何时接种疫苗以及谁仍然特别脆弱的决定。我们证明，既往感染的人在接种疫苗后，即使在第三次(加强)疫苗接种后，也会产生更好的抗体和T细胞反应。我们还表明，与短剂量间隔相比，辉瑞疫苗较长的剂量间隔可以产生更高的抗体应答和更低但更好的记忆质量T细胞应答。我们最新的工作表明，在接种两剂疫苗后，抗体反应在六个月内下降，但T细胞反应保持得很好，再次强化了T细胞对长期保护重要的想法。接种疫苗的人的T细胞仍然能很好地对抗Omicron变种，这种变种可以逃避人体大部分的中和抗体反应。我们已经与其他研究人员分享了我们的T细胞实验室技术，我们还与OCTIVE等国家研究团队合作，与我们更健康的医护人员群体相比，观察免疫问题患者的T细胞反应。我们现在正在申请资金，以维护我们为沥青财团建立的系统。我们需要对我们的医护人员进行跟踪，看看抗体和T细胞反应是否及时消退，并测量人们的免疫反应如何应对未来的病毒变异。我们也有机会更多地了解流感(流感)的免疫反应，因为由于新冠肺炎实施了限制措施，自2019/2020年冬季以来就没有任何流感在循环中。我们将与英国免疫学会合作，向医护人员和更广泛的公众解释我们的研究，并听取关于哪些是重要问题的意见。我们已经组建了一个高生产率的研究小组，并将利用PITCH2作为长期深入研究的跳板，以回答有关对SARS-CoV-2病毒和流感免疫的性质和持续时间的问题。

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.