Determining the potential universal applicability of a diurnal response to vaccination and the associated circadian immune processes

疫苗接种规划是全球公共卫生战略的核心内容，是预防各种威胁生命感染的关键。例如，流感疫苗接种是英国全科医生诊所开展的季节性疫苗接种计划的一部分，年龄在65岁以上的成年人占大多数。65岁以上的成年人现在也可以一次性接种肺炎和带状疱疹疫苗。尽管老年人很好地接种了这些疫苗（英国每年的流感疫苗接种率为70%），但65岁以上的人在流感相关的住院和死亡中所占比例最高，肺炎是英国第五大死因。这些数据表明，疫苗对老年人的效果较差，对31项研究的分析发现，老年人接种流感疫苗的效果在17-53%之间，而年轻人的效果为70-90%。因此，大多数老年人没有得到国家疫苗接种规划的充分保护，免受感染。对疫苗反应不佳的原因有很多，但一个主要因素是随着年龄的增长，免疫系统的功能变差了。该项目将研究一种改善老年人疫苗接种反应的新方法。在过去的十年里，人们已经清楚地认识到，免疫系统在一天中的不同时间工作得更好，它显示出昼夜节律。考虑到这一点，我们之前由MRC资助的项目进行了一项研究，研究在上午和下午接种流感疫苗是否会对疫苗的效果产生影响（血液中产生了多少抗体）。结果表明，疫苗在早上的效果明显更好，这为提高老年人的疫苗接种反应提供了一种成本中立和快速的方法。我们不知道的是，这种反应是否是流感疫苗独有的，以及一天中的时间效应是如何实现的。这个项目将检查一天中的时间对流感疫苗和肺炎疫苗Pneumovax 23的影响，这将使我们能够比较两种非常不同类型的疫苗（蛋白质和非蛋白质）的反应。这是很重要的，因为它将表明早晨接种疫苗的有益效果是否可以在各种蛋白质或非蛋白质性质的疫苗中看到。我们还将使用小鼠来确定一天中的时间如何影响免疫反应和我们产生抗体的能力，以增加我们对与公共卫生医学相关的免疫这一重要方面的理解。

Vaccination programmes are a core element of public health strategy worldwide and are key to preventing a wide range of life threatening infections. For example, the influenza vaccination is part of the seasonal vaccination programme carried out by GP surgeries across the UK, with adults aged 65+ years being the majority of recipients. Adults aged 65+ are also now offered a one off vaccination against pneumonia and shingles. Despite good uptake of these vaccinations among older adults (>70 % for the annual flu vaccination in the UK), the over 65s make up the highest proportion of the influenza-related hospitalisations and mortalities and Pneumonia is the 5th highest cause of death in the UK. These data suggest that the vaccines work less well in older adults and an analysis of 31 studies that measured the efficacy of the flu vaccination found in older adults this varied from 17-53%, compared with 70-90% in young adults. Most older adults are therefore not fully protected against infections by the national vaccination programme. There are many reasons for this poor response to vaccines, but a major factor is that the immune system functions less well as we age. This project will investigate a novel way to improve vaccination responses in older adults.It has become clear in the last decade that the immune system works better at different times of day, it shows a circadian rhythm. Bearing this in mind our previous project funded by MRC carried out a study looking at whether having the influenza vaccination in the morning versus the afternoon made a difference to how well the vaccine worked (how much antibody was produced in the blood). The results showed that the vaccine worked significantly better in the morning, which gives a cost neutral and quick way to improve vaccination responses in older adults. What we don't know is whether this response is unique to the influenza vaccine and how the time of day effect is achieved. This project will examine the time of day effect on the influenza vaccine and also the pneumonia vaccine Pneumovax 23, which will allow us to compare responses with two very different types of vaccine (protein and non protein). This is important as it will indicate whether the beneficial effect of morning vaccination might be seen in a wide range of vaccines which are either protein or non-protein in nature. We will also use mice to determine exactly how the time of day affects the immune response and our ability to produce antibody to increase our understanding of this important aspect of immunity relevant to public health medicine.