Yellow Fever Immune Response at Single Cell Resolution

Rockefeller University6 enrolled

Overview

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.

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.

Study Type

OBSERVATIONAL

Enrollment

Conditions

Healthy

Interventions

Yellow Fever VaccineDRUG

Yellow Fever Vaccine .5 ml

Eligibility

Sex: ALLMin age: 18 YearsMax age: 59 YearsHealthy volunteers:

Medical Language ↔ Plain English

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

Locations (1)

The Rockefeller University

New York, New York, United States

Outcomes

Primary Outcomes

Feasibility and accuracy of inDrop RNA-Seq

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.

Time frame: up to 42 days post baseline visit

Secondary Outcomes

Utility of inDrop RNA-Seq

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.

Time frame: Days 0, 3, 7, 14, 42

Data from ClinicalTrials.gov

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