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Turnover of Antigen Specific Lymphocytes After Immunization With the 17D Yellow Fever Vaccine

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.
 
ClinicalTrials.gov Identifier: NCT01290055
Recruitment Status : Active, not recruiting
First Posted : February 4, 2011
Last Update Posted : February 11, 2019
Sponsor:
Collaborators:
University of California, Berkeley
National Institutes of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Information provided by (Responsible Party):
Sri Edupuganti, MD MPH, Emory University

Brief Summary:

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 or disease Intervention/treatment Phase
Yellow Fever Biological: Yellow fever vaccine or YFV-17D Biological: Deuterium (70% enriched 2H2O) labeled water Not Applicable

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 50 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Official Title: Turnover of Antigen Specific Lymphocytes After Immunization With the 17D Yellow Fever Vaccine
Study Start Date : February 2011
Estimated Primary Completion Date : January 2020
Estimated Study Completion Date : January 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Fever

Arm Intervention/treatment
Experimental: Group 1
In group 1, participants will receive the Yellow fever vaccine or YFV-17D and will be asked to drink Deuterium (70% enriched 2H2O) labeled water for 2 weeks. They will undergo phlebotomy on Day 0, 14, 28 and 3 to 6 months, 1-2 years and >5 years after vaccination.
Biological: Yellow fever vaccine or YFV-17D
The YFV-17D (YF-VAX®) manufactured by Sanofi Pasteur as a one-dose vial will be purchased from the manufacturer. Vaccine will be stored at the Emory Investigational Drug service between 2o to 8o C as per the manufacturer's instructions. It will be transported to the Hope clinic per the Standard Operating Procedures.
Other Name: YF-VAX

Biological: Deuterium (70% enriched 2H2O) labeled water
70% enriched 2H2O will be obtained from Cambridge Isotope Laboratories (Andover, MA) in sterile 1L containers. An Emory IDS pharmacist will prepare sterile 50ml aliquots with a tamper seal which will be transported to the Hope clinic at room temperature.
Other Name: D20

Experimental: Group 2
In group 2, participants will receive the Yellow fever vaccine or YFV-17D and will be asked to drink Deuterium (70% enriched 2H2O) labeled water for 3 weeks. They will undergo phlebotomy on Day 0, 14, 28 and 3 to 6 months, 1-2 years and >5 years after vaccination.
Biological: Yellow fever vaccine or YFV-17D
The YFV-17D (YF-VAX®) manufactured by Sanofi Pasteur as a one-dose vial will be purchased from the manufacturer. Vaccine will be stored at the Emory Investigational Drug service between 2o to 8o C as per the manufacturer's instructions. It will be transported to the Hope clinic per the Standard Operating Procedures.
Other Name: YF-VAX

Biological: Deuterium (70% enriched 2H2O) labeled water
70% enriched 2H2O will be obtained from Cambridge Isotope Laboratories (Andover, MA) in sterile 1L containers. An Emory IDS pharmacist will prepare sterile 50ml aliquots with a tamper seal which will be transported to the Hope clinic at room temperature.
Other Name: D20




Primary Outcome Measures :
  1. Tracking of deuterium labeled CD28+/- subsets of tetramer positive yellow fever specific CD8 T cells [ Time Frame: CD8 T cells will be measured on Day 0, 14, 28 and 3 to 6 months, 1-2 years and >5 years after vaccination. ]
    Tracking of deuterium labeled CD28+/- subsets of tetramer positive yellow fever specific CD8 T cells

  2. Turnover rates of DCs and monocytes in response to YFV-17D vaccination using D20 [ Time Frame: CD8 T cells will be measured on Day 0, 14, 28 and 3 to 6 months, 1-2 years and >5 years after vaccination. ]
    Turnover rates of DCs and monocytes in response to YFV-17D vaccination using D20



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Ages Eligible for Study:   18 Years to 45 Years   (Adult)
Sexes Eligible for Study:   All
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
  6. Must agree not to receive any other vaccination during the labeling period with heavy water and in the first 28 days after receipt of yellow fever vaccination.

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

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 ClinicalTrials.gov identifier (NCT number): NCT01290055


Locations
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United States, Georgia
The Hope clinic of Emory Vaccine Center
Decatur, Georgia, United States, 30030
Sponsors and Collaborators
Sri Edupuganti, MD MPH
University of California, Berkeley
National Institutes of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Investigators
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Principal Investigator: Srilatha Edupuganti, MD Emory University
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Responsible Party: Sri Edupuganti, MD MPH, Associate Professor, Emory University
ClinicalTrials.gov Identifier: NCT01290055    
Other Study ID Numbers: IRB00046406
YFV Heavy Water Study ( Other Identifier: Other )
5U19AI057266 ( U.S. NIH Grant/Contract )
First Posted: February 4, 2011    Key Record Dates
Last Update Posted: February 11, 2019
Last Verified: February 2019
Keywords provided by Sri Edupuganti, MD MPH, Emory University:
Yellow Fever
Vaccine
Memory T Cells
Additional relevant MeSH terms:
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Yellow Fever
Fever
Body Temperature Changes
Signs and Symptoms
Arbovirus Infections
Virus Diseases
Flavivirus Infections
Flaviviridae Infections
RNA Virus Infections
Hemorrhagic Fevers, Viral