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-重债穷国第六年和第七年提出的研究将建立在已取得的相当大进展的基础上 在使用基于系统的方法理解分子网络驱动的前5年 对接种疫苗的先天和获得性免疫反应。第六年计划的主要工作重点 和7是了解最近获得许可的亚单位疫苗用于治疗的免疫学机制 带状疱疹(HZ，带状疱疹)对带状疱疹有非常有效的保护作用。赫兹，这是由 水痘带状疱疹病毒(VZV)每年影响全球数百万人，是一种重要的公众 关注老年人的健康。最近的一个重要进展是开发了一个新的亚基HZ 含有重组糖蛋白E亚单位的疫苗(“GE疫苗”)，辅以AS01，a 含有TLR4激动剂MPL和皂苷QS21(1-4)的脂质体佐剂系统。通用电气 疫苗最近已获准在50岁以上的受试者身上临床使用，商标为 Shingrix®。值得注意的是，即使在70岁的疫苗接种者(1-4岁)中，Shingrix®的疗效也很高(91%)。 尽管Shingrix®显示出卓越的抗体反应和更高的CD4+T细胞耐受性 对于GE疫苗的免疫应答，对GE疫苗的免疫应答的综合评估是 缺乏。这将在目标1和目标2中实现，我们将在其中分析先天和适应性反应 至Shingrix®。重要的是，我们将在之前的数据环境中分析这些结果 HIPC项目研究带状疱疹减毒活疫苗Zostavax®诱导的免疫反应。 目的1：系统分析Shingrix®在50-60岁和70岁人群中的先天反应 研究对象。 目的2：分析Shingrix®在50-59岁和70-85岁人群中诱导的获得性免疫反应 年龄较大的受试者。