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

Yellow Fever research study

What is the primary objective of this study?

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.

Who is eligible to participate?

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

Which medical condition, disease, disorder, syndrome, illness, or injury is researched?

Yellow Fever

Study Interventions

Interventions can include giving participants drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available or noninvasive approaches such as surveys, education, and interviews.

Biological:Yellow fever vaccine or YFV-17DThe 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.

Biological:Deuterium (70% enriched 2H2O) labeled water70% 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.

Study Arms

Research studies and clinical trials typically have two or more research arms. An arm is a group of people who receive the same treatment in the study.

Group 1In 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.

Group 2In 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.

Study Status

Active, not recruiting

Start Date: February 2011

Completed Date: January 2020

Phase: N/A

Type: Interventional


Primary Outcome: Tracking of deuterium labeled CD28+/- subsets of tetramer positive yellow fever specific CD8 T cells

Secondary Outcome:

Study sponsors, principal investigator, and references

Principal Investigator: Srilatha Edupuganti, MD

Lead Sponsor: Sri Edupuganti, MD MPH

Collaborator: University of California, Berkeley

More information:

Discuss Pyrexia