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

了解生命早期流感抗体库通过感染或疫苗印记

• 批准号: 10215742
• 负责人: Jiwon Lee
• 金额: $ 27.42万
• 依托单位: DARTMOUTH COLLEGE
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-07-01 至 2021-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10215742
• 关键词: Age; Antibodies; Antibody Repertoire; Antibody Response; Antigens; Child; Development; Effectiveness; Exposure to; Human; Immune response; Immune system; Immunity; Infection; Influenza; Influenza vaccination; Institutes; Life; Nature; Time; Vaccination; Vaccines; early childhood; imprint; improved; influenza virus vaccine; influenzavirus; response; vaccination strategy

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.

流感是一种持续存在的全球威胁，最紧迫的未满足需求是改善疫苗接种 策略更加有效，这从根本上取决于对疫苗介导的更好理解 由于流感的普遍性，人们会接触到流感。 病毒在很小的时候就存在，导致对第一次遇到的病毒的抗体反应早期发展 流感毒株 从通过感染或疫苗接种初次接触流感开始，就形成了最初的流感。 抗体库已经建立，并且在人的一生中不断重塑。 表明第一次暴露产生的初始抗体库被“印记”在免疫系统中 系统并对随后引发的抗体反应的性质产生重大影响 这种印记使免疫系统走上一条使免疫反应偏向后续的道路。 接触流感，并且人们越来越多地认识到儿童早期印记可能是 年度流感疫苗接种效果有限的原因本研究旨在描述流感疫苗接种效果有限的原因。 幼儿对流感的免疫反应及其对随后流感反应的影响 假设是，通过感染的第一次接触会导致更强的印记。 最初的流感抗体库比通过疫苗接种首次接触的要高。 目标 1，免疫。 曾有自然感染记录或有记录的儿童对流感疫苗的反应 将比较疫苗接种，重点关注从第一次超过 2 的时间点起抗体的持续性 在目标 2 中，包含印迹抗体库的抗体将在随后的疫苗接种中持续数年。 进行功能表征，以更好地了解印迹抗体的特征。 研究将有可能阐明控制印记的规则和机制，可用于 开发更好的疫苗免疫原以及疫苗接种策略。