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Yellow Fever Immune Response at Single Cell Resolution

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT03458780
Recruitment Status : Completed
First Posted : March 8, 2018
Last Update Posted : November 8, 2019
National Institute of Allergy and Infectious Diseases (NIAID)
Information provided by (Responsible Party):
Brad Rosenberg, Icahn School of Medicine at Mount Sinai

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.

Condition or disease Intervention/treatment
Healthy Drug: Yellow Fever Vaccine

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.

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Study Type : Observational
Estimated Enrollment : 6 participants
Observational Model: Case-Only
Time Perspective: Prospective
Official Title: Single Cell Transcriptomics for Characterizing the Human Immune Response to Yellow Fever Vaccination
Actual Study Start Date : August 22, 2016
Actual Primary Completion Date : September 5, 2018
Actual Study Completion Date : September 5, 2018

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Fever

Group/Cohort Intervention/treatment
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
Yellow Fever Vaccine .5 ml
Other Name: YF-Vax

Primary Outcome Measures :
  1. Feasibility and accuracy of inDrop RNA-Seq [ Time Frame: 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.

Secondary Outcome Measures :
  1. Utility of inDrop RNA-Seq [ Time Frame: 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.

Biospecimen Retention:   Samples With DNA
Research Bloods

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 59 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population
Healthy Volunteers

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT03458780

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United States, New York
The Rockefeller University
New York, New York, United States, 10065
Sponsors and Collaborators
Rockefeller University
National Institute of Allergy and Infectious Diseases (NIAID)
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Principal Investigator: Brad R Rosenberg, MD, PhD Icahn School of Medicine at Mount Sinai

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Responsible Party: Brad Rosenberg, Assistant Professor, Icahn School of Medicine at Mount Sinai Identifier: NCT03458780    
Other Study ID Numbers: BRO-0905
5U19AI111825 ( U.S. NIH Grant/Contract )
First Posted: March 8, 2018    Key Record Dates
Last Update Posted: November 8, 2019
Last Verified: November 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by Brad Rosenberg, Icahn School of Medicine at Mount Sinai:
yellow fever vaccine
immune response
droplet microfluidics single cell ("inDrop") RNA-Seq
Additional relevant MeSH terms:
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Yellow Fever
Arbovirus Infections
Vector Borne Diseases
Virus Diseases
Flavivirus Infections
Flaviviridae Infections
RNA Virus Infections
Hemorrhagic Fevers, Viral