System Biological Analyses of Innate and Adaptive Responses to Vaccination

对疫苗接种的先天和适应性反应的系统生物学分析

基本信息

批准号：
10201491
负责人：
Rafi Ahmed
金额：
$ 221.36万
依托单位：
EMORY UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-07-01 至 2023-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10201491
关键词：
Address Adjuvant Affect Agonist Antibody Response Antigens Attenuated Automobile Driving B-Lymphocytes Biological CD4 Positive T Lymphocytes Cells Clinical Clinical Trials Collaborations Data Data Set Development Elderly Gene Expression Profiling Glycoproteins Goals Herpes zoster disease Herpesvirus Type 3 Human Immune response Immunity Immunologics Innate Immune Response Investigation Liposomes Malaria Vaccines Memory Memory B-Lymphocyte Molecular Names Natural Immunity Pathway interactions Peripheral Blood Mononuclear Cell Plasmablast Population Public Health QS21 Recombinants Research Research Personnel Resolution Saponins Serum Subunit Vaccines System Systems Analysis Systems Biology T cell response T-Lymphocyte TLR4 gene Technology Vaccination Vaccines Virus Work Zoster Vaccine adaptive immune response age group base biological systems cytokine data management human very old age (85+)insight metabolomics novel vaccines response single cell technology vaccine efficacy

项目摘要

The research proposed in years 6 and 7 of the Emory-HIPC will build on the considerable progress made during the first 5 years in using systems based approaches to understand the molecular networks driving innate and adaptive immune responses to vaccination. The major focus of the work planned in years 6 and 7 is to understand the immunological mechanisms by which the recently licensed subunit vaccine for herpes zoster (HZ, shingles) induces highly efficacious protection against shingles. HZ which is caused by the varicella zoster virus (VZV), affects several million people/year globally, and is a significant public health concern for the elderly. An important recent development is the development of a new subunit HZ vaccine, which contains the recombinant glycoprotein E subunit (“gE vaccine”), adjuvanted with AS01, a liposome-based adjuvant system containing the TLR4 agonist MPL, and the saponin, QS21 (1-4). The gE vaccine has recently been licensed for clinical use in subjects older than 50 years, under the trade name Shingrix®. Remarkably, the efficacy of Shingrix® is high (91%) even in 70 year old vaccinees (1-4). Although Shingrix® has revealed superior antibody responses and greater durability of CD4+ T cell responses to the gE vaccine, a comprehensive assessment of immune responses to the gE vaccine is lacking. This will be achieved in Aims 1 and 2, where we will analyze the innate and adaptive responses to Shingrix®. Importantly we will analyze these results in the context of data generated from our previous HIPC project on immune responses induced by the live attenuated zoster vaccine, Zostavax®. Aim 1: Systems analysis of innate responses elicited by Shingrix® in 50-60 year old and >70 year old subjects. Aim 2: To analyze the adaptive immune response elicited by Shingrix® in 50-59 year old and >70-85 years old subjects.

埃默里重债穷国倡议第六年和第七年提出的研究将建立在已取得的重大进展的基础上在使用基于系统的方法来理解分子网络驱动的头 5 年里对疫苗接种的先天性和适应性免疫反应是第 6 年计划工作的主要重点。 7是了解最近获得许可的亚单位疫苗的免疫学机制带状疱疹（HZ，带状疱疹）可有效预防由带状疱疹引起的带状疱疹。水痘带状疱疹病毒 (VZV) 每年影响全球数百万人，是一种重要的公共疾病最近的一个重要进展是新亚基 HZ 的开发。疫苗，含有重组糖蛋白 E 亚基（“gE 疫苗”），佐以 AS01，一种基于脂质体的佐剂系统，含有 TLR4 激动剂 MPL 和皂苷 QS21 (1-4)。该疫苗最近已获准在 50 岁以上受试者中进行临床使用，商品名为 Shingrix® 值得注意的是，即使是已有 70 年历史的疫苗，Shingrix® 的功效也很高 (91%) (1-4)。尽管 Shingrix® 已展现出卓越的抗体反应和 CD4+ T 细胞的更高耐久性对 gE 疫苗的反应，对 gE 疫苗免疫反应的全面评估是这将在目标 1 和 2 中实现，我们将分析先天反应和适应性反应。重要的是，我们将在之前生成的数据的背景下分析这些结果。重债穷国项目关于由带状疱疹减毒活疫苗 Zostavax® 诱导的免疫反应。目标 1：Shingrix® 在 50-60 岁和 >70 岁人群中引起的先天反应的系统分析科目。目标 2：分析 Shingrix® 在 50-59 岁和 >70-85 岁人群中引发的适应性免疫反应岁的科目。