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Yellow Fever Immune Response at Single Cell Resolution

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赞助商
Rockefeller University
合作者
National Institute of Allergy and Infectious Diseases (NIAID)

关键词

抽象

The immune system is composed of diverse cell types with different functions that act together in order to defend against infection. This pilot study will test a new technology for studying these many different cell types at very large numbers at the level of individual cells. This method will then be used to identify the cell types and functions important for the immune response to the highly protective yellow fever vaccine, which will improve our understanding of effective vaccine features.

描述

Vaccines have had monumental impact in reducing the mortality and morbidity of infectious disease. However, the underlying immune mechanisms that contribute to their effectiveness are incompletely understood. Transcriptomics (methods that measure the activity of thousands of genes) studies have identified key features of responses to vaccination(see references) and infection(see references). However, these experiments are typically performed on heterogeneous cell mixtures such as peripheral blood mononuclear cells (PBMC which include certain types of white blood cells) and therefore provide an aggregate measure of gene expression from the many different immune cells and their respective activities in the mixture. Such results can obscure important biological information, particularly in minor subsets of active cells. Establishing a method for immune transcriptomics at single cell resolution would be a highly significant advance and enable more informative and functionally relevant systems immunology studies with commonly used sample types (i.e. PBMC). Applying this high-resolution approach to Yellow Fever Vaccine (YFV), an exceptionally effective vaccine, is likely to identify unappreciated mechanisms that contribute to protective immunity.

日期

最后验证: 10/31/2019
首次提交: 03/01/2018
提交的预估入学人数: 03/01/2018
首次发布: 03/07/2018
上次提交的更新: 11/05/2019
最近更新发布: 11/07/2019
实际学习开始日期: 08/21/2016
预计主要完成日期: 09/04/2018
预计完成日期: 09/04/2018

状况或疾病

Healthy

干预/治疗

Drug: Yellow Fever Vaccine Participant

-

手臂组

干预/治疗
Yellow Fever Vaccine Participant
Healthy participants who receive the Yellow fever vaccine for travel and/or occupational risk will have peripheral blood samples collected longitudinally at time points selected for different immune events post-vaccination according to published studies (Day 0 baseline; Days: 3, 7, 14, and 42).
Drug: Yellow Fever Vaccine Participant
Yellow Fever Vaccine .5 ml

资格标准

有资格学习的年龄 18 Years 至 18 Years
有资格学习的性别All
取样方式Non-Probability Sample
接受健康志愿者
标准

Inclusion Criteria:

- Male or female between the ages of 18 and 59 years old

- Volunteers who have not received a vaccination within 30 days of the YFV and do not anticipate to receive a vaccination within 30 days

- Volunteers who are seeking the YFV for either travel reasons or occupational risk

- Volunteers willing to undergo one screening visit, one visit to receive the YFV, and four post-vaccination visits

- Volunteers without medical conditions who are willing to give blood once for the development of the inDrop technique

Exclusion Criteria:

- Male or females under 18 or over 59 years of age

- Volunteers who received other vaccination less than 30 days prior to receiving the YFV

- Volunteers with acute or febrile disease

- Volunteers unable to return for the post vaccination follow-up visits

- Volunteers with an allergy to eggs, chicken proteins, gelatin, or other components of the Yellow Fever vaccine

- Participation in another clinical study of an investigational product currently or within the past 90 days, or expected participation during this study

- Is pregnant or lactating

- Volunteers with a history of yellow fever vaccination and/or infection

- Volunteers with a history of viral hepatitis and/or non-viral liver disease

- In the opinion of the investigators, the volunteer is unlikely to comply with the study protocol

- Immunosuppressed individuals as a result of cancer, transplantation, and or primary immunodeficiency

- Immunosuppressed individuals as a result of medications (such as high-dose systemic corticosteroids, alkylating drugs, antimetabolites, TNF-α inhibitors (e.g., etanercept), IL-1 blocking agents (e.g., anakinra), and other monoclonal antibodies targeting immune cells (e.g.,rituximab, alemtuzumab) and/or radiation

- Volunteers with thymus disorders (including myasthenia gravis, Di George syndrome, or thymoma) and/or history of thymectomy

- Individuals infected with HIV

结果

主要结果指标

1. Feasibility and accuracy of inDrop RNA-Seq [up to 42 days post baseline visit]

The feasibility and accuracy of inDrop RNA-Seq for distinguishing different cell types will be assessed by comparing (for concordance) cell subset population frequency and distribution values determined by inDrop RNA-seq to cell subset population frequency and distribution values determined by flow cytometry immunophenotyping, the present "gold standard" technique.

次要成果指标

1. Utility of inDrop RNA-Seq [Days 0, 3, 7, 14, 42]

The utility of inDrop RNA-Seq for characterizing an immune response will be determined by measuring cell subset frequencies and gene expression profiles at single cell resolution over time following YFV.

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