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: 10345981
• 负责人: Rafi Ahmed
• 金额: $ 46.64万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-03-01 至 2022-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10345981
• 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.

Emory-Ihipc的第6年和7年级提出的研究将基于取得的重大进展 在最初的5年中，使用基于系统的方法来了解分子网络驱动 先天和适应性免疫调查以进行疫苗接种。计划在6年内计划工作的主要重点 7是要了解最近许可的亚基疫苗的免疫机制 疱疹带状疱疹（Hz，带状疱疹）可诱导针对带状疱疹的高效保护。 Hz是由 水痘带状疱疹病毒（VZV）在全球范围内影响数百万人，并且是一个重要的公众 老年人的健康关注。最近的一个重要发展是开发新的亚基HZ 疫苗包含重组糖蛋白E亚基（“ GE疫苗”），并用AS01，A调节 基于脂质体的调节系统含有TLR4激动剂MPL和皂苷QS21（1-4）。 GE 疫苗最近获得了50岁以上受试者的临床用途，以商品名称 Shingrix®。值得注意的是，即使在70岁的疫苗（1-4）中，Shingrix®的效率也很高（91％）。 尽管Shingrix®揭示了CD4+ T细胞的优质抗体响应和更大的耐用性 对GE疫苗的反应，对GE疫苗的免疫反应的全面评估是 缺乏。这将在目标1和2中实现，我们将分析先天和适应性的反应 到Shingrix®。重要的是，我们将在我们以前的数据中分析这些结果 HIPC针对活带状疫苗Zostavax®引起的免疫反应的HIPC项目。 AIM 1：Shingrix®在50 - 60岁且> 70岁的Shingrix®引起的先天响应的系统分析 主题。 目标2：分析Shingrix®在50-59岁时引起的自适应免疫调节和> 70-85 年历史的主题。