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

• 批准号: 10056675
• 负责人: Rafi Ahmed
• 金额: $ 240.49万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-07-01 至 2022-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10056675
• 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

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6年和第7年拟议的研究将以已取得的重大进展为基础 在使用基于系统的方法来理解分子网络驱动的前5年中， 对疫苗接种的先天性和适应性免疫应答。未来几年计划的工作重点6 和7是了解最近批准的亚单位疫苗的免疫机制， 带状疱疹（HZ，带状疱疹）诱导针对带状疱疹的高效保护。HZ由以下因素引起 水痘带状疱疹病毒（VZV）每年影响全球数百万人，是一种重要的公共病毒， 关注老年人的健康。一个重要的最近发展是一个新的亚基HZ的发展 疫苗，其含有重组糖蛋白E亚单位（“gE疫苗”），用AS 01作为佐剂， 含有TLR 4激动剂MPL和皂苷QS 21的基于脂质体的佐剂系统（1-4）。的gE 疫苗最近被许可用于50岁以上的受试者的临床使用，商品名为 Shingrix®。值得注意的是，即使在70岁的接种者（1-4岁）中，Shingrix®的有效性也很高（91%）。 尽管Shingrix®已经显示出上级抗体应答和更大的CD 4 + T细胞耐受性， gE疫苗免疫应答的综合评估， 缺乏这将在目标1和目标2中实现，我们将分析先天和适应性反应， 到Shingrix®。重要的是，我们将分析这些结果的背景下产生的数据，从我们以前的 关于带状疱疹减毒活疫苗Zostavax®诱导的免疫应答的HIPC项目。 目的1：系统分析Shingrix®在50-60岁和>70岁人群中引发的先天反应 科目 目的2：分析Shingrix®在50-59岁和>70-85岁人群中引发的适应性免疫应答 岁的科目。