Clinical trial NCT03458780: Yellow Fever Immune Response at Single Cell Resolution
Official title: Single Cell Transcriptomics for Characterizing the Human Immune Response to Yellow Fever Vaccination
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Healthy
Keywords: yellow fever vaccine
immune response
droplet microfluidics single cell ("inDrop") RNA-Seq
Lead sponsor: Rockefeller University
Sponsor class: OTHER
Collaborators: name: National Institute of Allergy and Infectious Diseases (NIAID)
First posted: 2018-03-08
Enrollment: 6
Sex: ALL
Minimum age (years): 18
Maximum age (years): 59
Standard ages: ADULT
Accepts healthy volunteers: yes
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Healthy Volunteers

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Feasibility and accuracy of inDrop RNA-Seq
timeFrame: up to 42 days post baseline visit
Secondary outcomes:
measure: Utility of inDrop RNA-Seq
timeFrame: Days 0, 3, 7, 14, 42
Other outcomes:
Locations:
city: New York
country: United States
facility: The Rockefeller University
state: New York
Study officials:
affiliation: Icahn School of Medicine at Mount Sinai
name: Brad R Rosenberg, MD, PhD
role: PRINCIPAL_INVESTIGATOR
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