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: 10375723
• 负责人: Rafi Ahmed
• 金额: $ 46.77万
• 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 2023-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10375723
• 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 对疫苗接种的先天和适应性免疫反应。第六年计划工作重点 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）可有效预防带状疱疹。 HZ 是由 水痘带状疱疹病毒 (VZV) 每年影响全球数百万人，是一种重要的公共疾病 关心老年人的健康。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”），并以 AS01 为佐剂， 基于脂质体的佐剂系统，含有 TLR4 激动剂 MPL 和皂苷 QS21 (1-4)。基因E 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，即使对于 70 岁的疫苗接种者 (1-4)，Shingrix® 的功效也很高 (91%)。 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 缺乏。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 到 Shingrix®。重要的是，我们将在我们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：对 Shingrix® 在 50-60 岁和 >70 岁人群中引起的先天反应进行系统分析 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。

项目成果

Liver fibrosis occurs through dysregulation of MyD88-dependent innate B-cell activity.

• DOI: 10.1002/hep.27761
• 发表时间: 2015-06
• 期刊: HEPATOLOGY
• 影响因子: 13.5
• 作者: Thapa, Manoj;Chinnadurai, Raghavan;Velazquez, Victoria M.;Tedesco, Dana;Elrod, Elizabeth;Han, Jin-Hwan;Sharma, Prachi;Ibegbu, Chris;Gewirtz, Andrew;Anania, Frank;Pulendran, Bali;Suthar, Mehul S.;Grakoui, Arash
• 通讯作者: Grakoui, Arash

Zika Virus Infects Human Placental Macrophages.

• DOI: 10.1016/j.chom.2016.05.015
• 发表时间: 2016-07-13
• 期刊: Cell host & microbe
• 影响因子: 30.3
• 作者: Quicke KM;Bowen JR;Johnson EL;McDonald CE;Ma H;O'Neal JT;Rajakumar A;Wrammert J;Rimawi BH;Pulendran B;Schinazi RF;Chakraborty R;Suthar MS
• 通讯作者: Suthar MS

Immunogenomics and systems biology of vaccines.

• DOI: 10.1111/j.1600-065x.2010.00971.x
• 发表时间: 2011-01
• 期刊: Immunological reviews
• 影响因子: 8.7
• 作者: Buonaguro L;Pulendran B
• 通讯作者: Pulendran B

Broadly reactive human CD8 T cells that recognize an epitope conserved between VZV, HSV and EBV.

识别VZV，HSV和EBV之间保守的表位的广泛反应性人CD8 T细胞。

• DOI: 10.1371/journal.ppat.1004008
• 发表时间: 2014-03
• 期刊: PLoS pathogens
• 影响因子: 6.7
• 作者: Chiu C;McCausland M;Sidney J;Duh FM;Rouphael N;Mehta A;Mulligan M;Carrington M;Wieland A;Sullivan NL;Weinberg A;Levin MJ;Pulendran B;Peters B;Sette A;Ahmed R
• 通讯作者: Ahmed R

Network-based modular latent structure analysis.

• DOI: 10.1186/1471-2105-15-s13-s6
• 发表时间: 2014
• 期刊: BMC bioinformatics
• 影响因子: 3
• 作者: Yu T;Bai Y
• 通讯作者: Bai Y