Role of the microbiome in HIV vaccine induced heterogeneity

微生物组在 HIV 疫苗诱导异质性中的作用

基本信息

批准号：
9753908
负责人：
James G. Kublin
金额：
$ 73.97万
依托单位：
FRED HUTCHINSON CANCER RESEARCH CENTER
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-09-27 至 2021-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9753908
关键词：
Adjuvant Adult Africa South of the Sahara Age Antibodies Bacteria Bacteroides fragilis Butyrates Clinical Communities Comorbidity Complex Data Development Ecosystem Flagellin Future Gender Germ-Free Gnotobiotic HIV Infections HIV vaccine Heterogeneity Homeostasis Human Human Microbiome Immune Immune response Immune system Immunity Immunization Immunoglobulin Class Switching Individual Intervention Knowledge Learning Ligands Light Mediating Memory B-Lymphocyte Microbe Mus Pathway interactions Population Heterogeneity Regimen Research Project Grants Risk Role Sampling Shapes Signal Transduction Statistical Methods Structure of germinal center of lymph node System TLR5 gene Vaccines Validation Volatile Fatty Acids Work adaptive immune response base case control efficacy study germ free condition gut microbiome gut microbiota immunogenicity improved interest metabolomics microbial microbiome microbiota mouse model novel pathogen receptor reconstitution response vaccine candidate vaccine development vaccine response

项目摘要

The incredible diversity and abundance of the human microbiome has only come to light in the last decade. The scientific community has learned that the gut microbial ecosystem has a major role in the development and homeostasis of the immune system. Our team wants to learn how these systems communicate to shape HIV vaccine immune responses. We are interested in how the microbiome shapes immune responses to HIV vaccines and contributes to vaccine response heterogeneity. We have a special emphasis on investigating the durability and class of antibodies that are elicited by different vaccines and the cellular responses that may contribute to these humoral endpoints, and how specific microbiota may contribute to these different responses. We will conduct correlates analyses with clinical and mouse microbiome and immunogenicity data; we will unravel mechanisms of immunity by perturbation of the immune system and the microbiome — the immune system via multiple adjuvanted immunization regimens and the microbiome by gut microbial reconstitution in germ free mice; and we will conduct metabolomics case-control analyses from select human and mouse samples. The knowledge gained in the end will shed light on the mechanisms of how vaccines work and may improve vaccines by way of novel adjuvant discovery.

人类微生物组的令人难以置信的多样性和抽象仅浮出水面在过去的十年中。科学界了解了肠道微生物生态系统在免疫的发育和稳态中具有重要作用系统。我们的团队想了解这些系统如何沟通以塑造艾滋病毒疫苗免疫备受调查。我们对微生物组如何形成免疫感兴趣对HIV疫苗的反应并有助于疫苗反应异质性。我们有特别强调调查抗体的耐用性和类别通过不同的疫苗和可能导致这些疫苗的细胞反应引起的体液终点，以及特定的微生物群如何对这些不同的贡献回答。我们将进行与临床和小鼠微生物组和小鼠微生物组的分析以及免疫原性数据；我们将通过扰动来阐明免疫学的机制免疫系统和微生物组 - 通过多个调整后的免疫系统免疫方案和微生物组的微生物组，无菌菌小鼠；我们将从某些人类和鼠标样品。最终获得的知识将阐明疫苗的工作原理，并可以通过新颖的调整发现改善疫苗。