Turnover of Antigen Specific Lymphocytes After Immunization With the Yellow Fever Vaccine

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2014 by Emory University
Sponsor:
Collaborator:
University of California, Berkeley
Information provided by (Responsible Party):
Sri Edupuganti, MD MPH, Emory University
ClinicalTrials.gov Identifier:
NCT01290055
First received: February 3, 2011
Last updated: May 22, 2014
Last verified: May 2014
  Purpose

The yellow fever vaccine is a live, attenuated virus that results in a robust immune response, especially in the T cell compartment. We have been studying immune responses to live viral infections using the yellow fever vaccine as a model for a live viral infection. In this study, we are interested in looking at the processing and lifespan of yellow fever specific CD8 T cells.

We plan to accomplish this by measuring DNA replication and cell proliferation in humans using a naturally occurring stable isotope called deuterium (D20). This technique has been used to track the turnover of a number of human cell types in vivo. We plan to use D20 labeling to track YFV specific CD8+ T cells in human vaccinees who are positive for a specific HLA type, HLA A202.

Deuterium labeled water (D2O), also known as heavy water is physically and chemically very similar to ordinary drinking water. In water, two hydrogen atoms bond to an oxygen and create H20. However in deuterated water, deuterium atoms replace the hydrogen atoms. Deuterium is a form of hydrogen that has an extra neutron. This neutron gives the atom extra weight, hence the name "heavy water." This extra weight can be detected in the lab with very sensitive instruments. Scientists have been using heavy water as a tracer to gain a better understanding of animal and human metabolic rates. Deuterium is in fact already in the water we drink daily. It is not radioactive, and it occurs naturally at a concentration of about 1 part per 5,000. Researchers have used heavy water since 1934 as a safe and effective tool in clinical trials.


Condition Intervention
Yellow Fever
Biological: Yellow fever vaccine
Biological: Yellow fever vaccine and D20 water

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Basic Science
Official Title: Turnover of Antigen Specific Lymphocytes After Immunization With the 17D Yellow Fever Vaccine

Resource links provided by NLM:


Further study details as provided by Emory University:

Primary Outcome Measures:
  • To evaluate the life span and decay curve of effector CD8 T cells after immunization with 17D yellow fever vaccine [ Time Frame: CD8 T cells will be measured on days 14, 21 and at weeks 6, 10, 14, 18, 22, 26, 32, 36, 40, 44, 48 and 52 after vaccination ] [ Designated as safety issue: No ]
    The life span and decay curve of yellow specific effector CD8 T cells will be detected by deuterium labeling

  • To evaluate the rate of homeostatic turnover of memory CD8 T cells after immunization with 17D yellow fever vaccine [ Time Frame: CD8 T cells will be measured on days 14, 28, weeks 8,9,,10,11,12, 24, 25, 26, 27 , 28 after vaccination ] [ Designated as safety issue: No ]

Estimated Enrollment: 40
Study Start Date: February 2011
Estimated Study Completion Date: September 2015
Estimated Primary Completion Date: September 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Group 1
In group 1, participants will receive the Yellow fever vaccine and will be asked to drink deuterium labeled water for 2 weeks. They will undergo phlebotomy on days 0, 14, 21, weeks 6, 10, 14, 18, 22, 26, 32, 36, 40, 44, 48 and 52.
Biological: Yellow fever vaccine
Group 1: All participants will receive the yellow fever vaccine and will be asked to drink deuterium labeled water and will undergo serial blood draws over 1 year.
Other Name: YF-VAX
Experimental: Group 2
All participants in Group 2 will receive the yellow fever vaccine and will drink deuterium labeled for 3 weeks and will undergo serial phlebotomy for upto 7 months.
Biological: Yellow fever vaccine and D20 water
Eligible participants will receive the yellow fever vaccine and will drink D20 water
Other Name: YF-VAX

  Eligibility

Ages Eligible for Study:   18 Years to 45 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  1. Able to understand and give informed consent
  2. Age 18-45 years
  3. Participants agree not to take any live vaccines 30 days before or after (14 days for inactivated) yellow fever vaccination
  4. Women of child bearing potential must agree to use effective birth control for at least 2 months after yellow fever vaccination. A negative urine pregnancy test must be documented prior to vaccination and prior to the initiation of drinking deuterium labeled water.
  5. Must be positive for the HLA A202 allele

Exclusion Criteria:

  1. Travel to or having lived in a country/area which is endemic for yellow fever
  2. History of previous yellow fever, West Nile, Dengue, St. Louis encephalitis, Japanese encephalitis vaccination or infection
  3. Any history of allergy to eggs, chicken or gelatin or to any previous vaccine
  4. A history of a medical condition resulting in impaired immunity (such as HIV infection, cancer, particularly leukemia, lymphoma, use of immunosuppressive or antineoplastic drugs or X-ray treatment). Persons with previous skin cancers or cured non-lymphatic tumors are not excluded from the study.
  5. History of HIV infection, Hepatitis B or Hepatitis C infection
  6. History of any chronic medical conditions that are considered progressive (ex, diabetes, heart disease, lung disease, liver disease, kidney disease, gastrointestinal diseases and uncontrolled hypertension). Use of systemic immunosuppressive medications (ex, prednisone) for 2 weeks or more in the past 3 months
  7. History of excessive alcohol consumption, drug abuse, psychiatric conditions, social conditions or occupational conditions that in the opinion of the investigator would preclude compliance with the trial
  8. Thymus gland problems (such as myasthenia gravis, DiGeorge syndrome, thymoma) or removal of thymus gland or history of autoimmune disorder.
  9. Recipient of a blood products or immune globulin product within 42 days of the vaccination visit
  10. Pregnant women and nursing mothers or women who are planning to become pregnant within 2 months after receiving the yellow fever vaccination.
  11. Any condition in the opinion of the investigator that would interfere with the proper conduct of the trial
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01290055

Contacts
Contact: Eileen Osinski 404-727-8435 gosinsk@emory.edu
Contact: Shashi Nagar 404-712-1407 shashi.nagar@emory.edu

Locations
United States, Georgia
The Hope clinic of Emory Vaccine Center Recruiting
Decatur, Georgia, United States, 30030
Contact: Eileen Osinski    404-727-8435    gosinsk@emory.edu   
Sponsors and Collaborators
Sri Edupuganti, MD MPH
University of California, Berkeley
Investigators
Principal Investigator: Srilatha Edupuganti, MD Emory University
  More Information

No publications provided

Responsible Party: Sri Edupuganti, MD MPH, Assistant Prfessor, Emory University
ClinicalTrials.gov Identifier: NCT01290055     History of Changes
Other Study ID Numbers: IRB00046406, YFV heavy water study
Study First Received: February 3, 2011
Last Updated: May 22, 2014
Health Authority: United States: Federal Government
United States: Food and Drug Administration
United States: Institutional Review Board

Keywords provided by Emory University:
yellow fever
vaccine
memory T cells

Additional relevant MeSH terms:
Fever
Yellow Fever
Body Temperature Changes
Signs and Symptoms
Arbovirus Infections
Virus Diseases
Flavivirus Infections
Flaviviridae Infections
RNA Virus Infections
Hemorrhagic Fevers, Viral

ClinicalTrials.gov processed this record on August 28, 2014