Yellow Fever Immune Response at Single Cell Resolution

November 6, 2019 updated by: Brad Rosenberg, Rockefeller University

Single Cell Transcriptomics for Characterizing the Human Immune Response to Yellow Fever Vaccination

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Observational

Enrollment (Anticipated)

6

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • New York
      • New York, New York, United States, 10065
        • The Rockefeller University

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 59 years (Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

Healthy Volunteers

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

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 Names:
  • YF-Vax

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
up to 42 days post baseline visit

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
Days 0, 3, 7, 14, 42

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Rockefeller University

Collaborators

National Institute of Allergy and Infectious Diseases (NIAID)

Investigators

  • Principal Investigator: Brad R Rosenberg, MD, PhD, Icahn School of Medicine at Mount Sinai

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

August 22, 2016

Primary Completion (Actual)

September 5, 2018

Study Completion (Actual)

September 5, 2018

Study Registration Dates

First Submitted

March 2, 2018

First Submitted That Met QC Criteria

March 2, 2018

First Posted (Actual)

March 8, 2018

Study Record Updates

Last Update Posted (Actual)

November 8, 2019

Last Update Submitted That Met QC Criteria

November 6, 2019

Last Verified

November 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • BRO-0905
  • 5U19AI111825 (U.S. NIH Grant/Contract)

Drug and device information, study documents

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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