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

基本信息

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
项目类别：
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

项目摘要

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.

流感是一个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更有效的策略，基本呈现对疫苗的更好理解人类的免疫力。病毒在很小的时候，抗体对第一个遇到的抗体反应的早期发育流感菌株从初始接触流感，最初的流感建立了抗体曲目，并且在最近的研究中包含了抗体建议通过第一次曝光产生的植物抗体是“印象”的免疫系统并对随后引起的抗体反应的性质产生重大影响挑战。对流感的曝光，这是一首越来越多的歌曲，幼儿印迹可能是年度流感疫苗接种有限有效的原因。幼儿对流感的免疫反应ATS ETS ETS ETS ETS ETS ETS ETS ETS对随后对流感的反应疫苗接种。初始流感抗体比第一次暴露在AIM 1中。对先前自然感染或事先记录的儿童中流感疫苗的反应将比较疫苗接种，重点是抗体的持久性，从第一个时间点以上的第一个时间点开始随后的疫苗接种。在功能上表征以更好地了解印迹抗体的特征。研究可能会阐明有关印记的规定和机制，可以将其利用到开发更好的疫苗免疫原和疫苗接种策略。