Understanding Early-life Influenza Antibody Repertoire Imprinting Through Infection or Vaccination

流感是一个持续的全球威胁，最迫切的未满足需求是改善疫苗接种 更有效的策略，这从根本上取决于对疫苗介导的 人类的免疫力。由于流感的普遍性，人们会接触到流感 病毒在早期的年龄，导致早期发展的抗体反应，以第一次遇到 流感病毒株从最初通过感染或接种疫苗接触流感开始， 抗体库建立起来，并在人的一生中不断重塑。最近的研究 这表明，从第一次接触产生的初始抗体库是“印记”在免疫系统中， 系统，并对随后引起的抗体应答的性质产生重大影响。 挑战这种印记使免疫系统走上了一条使免疫反应偏向于随后的免疫反应的道路。 接触流感，并且越来越多的人认识到，儿童早期的印记可能是 每年流感疫苗接种效果有限的原因。本研究旨在描述 幼儿对流感免疫应答及其对流感后续应答的影响 预防针这一假设是，通过感染的第一次接触导致更强的印记， 初始流感抗体库比通过疫苗接种的首次暴露。目标1：免疫 记录既往自然感染或记录既往 将比较疫苗接种，重点是从第一个时间点开始抗体的持续性超过2 多年的疫苗接种。在目的2中，包含印迹抗体库的抗体将 进行功能表征，以更好地了解印迹抗体的特征。总的来说，这 这项研究将可能阐明管理印记的规则和机制，这些规则和机制可以被利用到 开发更好的疫苗免疫原以及疫苗接种策略。

Influenza is a persisting global threat, and the most pressing unmet need is to improve vaccination strategies to be more effective, with this fundamentally hinging on a better understanding of vaccinemediated immunity in humans. Due to the ubiquitous nature of influenza, people are exposed to influenza virus at an early age, resulting in the early development of antibody responses to the first encountered influenza strains. From this initial exposure to influenza via infection or vaccination, the initial influenza antibody repertoire is established, and it is constantly reshaped during one’s lifetime. Recent studies have suggested that this initial antibody repertoire generated from the first exposure is ‘imprinted’ in the immune system and exerts a major influence on the nature of the antibody response elicited upon subsequent challenges. Such imprinting sets the immune system on a path that bias immune responses to subsequent exposures to influenza, and there is an increasing understanding that early childhood imprinting might be the reason for the limited effectiveness of the annual flu vaccination. This study aims to characterize the immune response to influenza in young children and its effect on subsequent responses to influenza vaccination. The hypothesis is that that the first exposure through infection results in stronger imprinting of initial influenza antibody repertoire than the first exposure through vaccination. In Aim 1, the immune response to influenza vaccine in children who had documented prior natural infection or documented prior vaccination will be compared, focusing on the persistence of the antibodies from the first time point over 2 years of subsequent vaccinations. In Aim 2, the antibodies comprising the imprinted antibody repertoire will be functionally characterized to better understand the features of the imprinted antibodies. Collectively, this study will potentially elucidate the rules and mechanisms governing imprinting, which can be leveraged into the development of better vaccine immunogens as well as vaccination strategies.