Childhood evolution of B cell responses to COVID-19 vaccination

尽管有几种有效的疫苗被批准用于成人，但针对18岁以下儿童的COVID-19疫苗开发所花的时间比成人更长。这部分是因为研究人员在儿童中进行大规模疫苗试验时面临的伦理和后勤挑战，特别是在低收入和中等收入国家。美国药品和医疗保健管理局宣布，他们将接受使用成人疫苗试验数据来假设疫苗在年轻人中的有效性，这将减少我们在许可疫苗时需要从年轻人那里收集的试验数据量。然而，这种方法依赖于这样的假设，即儿童对COVID-19疫苗接种的免疫反应的性质与成人相同。我们目前对儿童后期疫苗接种的免疫反应如何变化的理解是有限的，因为大多数研究以前都是关于婴儿期的免疫反应，当时儿童在短时间内接受了许多儿童疫苗。我们可以通过两种方法来研究疫苗接种的抗体反应，首先是通过观察抗体对引起COVID-19的SARS-CoV-2的特异性如何，其次是它们如何触发针对该病毒的保护性免疫反应。B细胞是产生抗体的一种特殊类型的白色血细胞。对这些细胞的遗传分析表明，它们产生特异性抗体的能力在儿童期不如成年期发育得好。儿童COVID-19疾病后的抗体效应子功能已被证明与成人不同，但尚不清楚疫苗接种是否也是如此。这两个因素是否意味着儿童对COVID-19疫苗接种的反应与成人有显著差异尚不清楚。在这个项目中，我们将使用一种新开发的方法来了解抗体识别SARS-CoV-2的能力如何随着儿童晚期的年龄而变化。我们将使用现代遗传分析，它可以在单个细胞水平上观察细胞，以了解每个白色血细胞产生的抗体类型。这将给我们以前无法收集的知识，关于儿童时期抗体结构如何随年龄变化。我们还将使用免疫细胞激活的荧光标记来测量抗体如何有效地激活其他免疫细胞。进一步的分析将使我们能够确定儿童的免疫反应是否与成人直接可比，或者当我们使用成人数据来预测疫苗在儿童中的有效性时是否需要进行调整。这将提高我们对儿童后期抗体成熟的理解，这不仅与疫苗反应有关，而且与免疫相关的其他领域，包括对感染和自身免疫性疾病的反应。

COVID-19 vaccine development for children aged under 18 has taken longer than for adults, despite several effective vaccines being approved for use in adults. This is partly because of the ethical and logistic challenges researchers face when running large-scale vaccine trials in children, particularly in low and middle-income country settings. The Medicines and Healthcare Regulatory Agency has announced that they will accept the use of adult vaccine trial data to make assumptions about the effectiveness of vaccines in young people, which will reduce the amount of trial data we need to collect from young people when licensing a vaccine. However, this approach relies on the assumption that the nature of the immune response to COVID-19 vaccination in children is the same in adults. Our current understanding of how immune responses to vaccination change in late childhood is limited, as most research has previously been on immune responses in infancy, when children receive many childhood vaccines in a short space of time. There are two ways in which we can investigate antibody responses to vaccination, firstly by looking at how specific the antibodies are against SARS-CoV-2, the virus which causes COVID-19, and secondly, how well they trigger a protective immune response against the virus. B cells are a specialised type of white blood cell which produce antibody. Genetic analysis of these cells has shown that their ability to produce specific antibodies is less well developed in childhood than in adulthood. Antibody effector functions following COVID-19 disease in children have been shown to be different to those in adults, but it is not known whether this is also true for vaccination. Whether these two factors mean that childhood responses to COVID-19 vaccination are significantly different from adults is unknown. In this project we will use a newly developed approach to understand how the ability of antibodies to recognise SARS-CoV-2 changes with age over late childhood. We will use modern genetic analysis which can look at cells at the individual cell level to see what type of antibody each white blood cell is making. This will give us knowledge that we have not previously been able to collect, about how antibody structure in childhood changes with age. We will also use tests which measure how effectively antibodies activate other immune cells using fluorescent markers of immune cell activation. Further analysis will enable us to identify whether the immune response in children is directly comparable with adults or whether adjustments need to be made when we use adult data to predict how effective vaccines are in children. This will improve our understanding of antibody maturation in late childhood which is relevant not only to vaccine responses but other areas related to immunity including response to infection and autoimmune diseases.