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

NCT01290055 | Completed Phase 4 FDA Drug

• 2 other identifiers: IRB00046406U19AI057266
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 1

Brief Summary

The yellow fever vaccine is a live, attenuated virus that results in a robust immune response, especially in the T cell compartment. The researchers 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, the researchers are interested in looking at the processing and lifespan of yellow fever specific CD8 T cell by measuring DNA replication and cell proliferation in humans using a naturally occurring stable isotope called deuterium.

Conditions

Yellow Fever

Keywords

Yellow Fever; Vaccine; Memory T Cells

Outcome Measures

Primary Outcomes (5)

• Lifespan of Effector CD8 T Cells

  The life span of effector CD8 T cells after immunization with 17D yellow fever vaccine is measured in days. The schedule of follow up visits depends on the study arm that the participant is in.

  Up to Month 12

• Decay Curve of Effector CD8 T Cells

  The decay curve of effector CD8 T cells after immunization with 17D yellow fever vaccine is measured in days. The schedule of follow up visits depends on the study arm that the participant is in.

  Up to Month 12

• Homeostatic Turnover of Memory CD8 T Cells

  The rate of homeostatic turnover of memory CD8 T cells after immunization with 17D yellow fever vaccine. The schedule of follow up visits depends on the study arm that the participant is in.

  Up to Month 12

• Lifespan of Monocytes

  The life span of monocytes after immunization with 17D yellow fever vaccine is measured in days. The schedule of follow up visits depends on the study arm that the participant is in.

  Up to Month 12

• Decay Curve of Monocytes

  The decay curve of monocytes after immunization with 17D yellow fever vaccine is measured in days. The schedule of follow up visits depends on the study arm that the participant is in.

  Up to Month 12

Secondary Outcomes (8)

• Magnitude of T Cell Responses

  Up to Month 12

• Kinetics of T Cell Responses

  Up to Month 12

• Magnitude of B Cell Responses

  Up to Month 12

• Kinetics of B Cell Responses

  Up to Month 12

• Turnover of Epstein-Barr Virus (EBV)-Specific CD8 T Cells

  Up to Month 12

Study Arms (8)

Group 1a - Drink deuterated water on days 0 - 14 post-vaccination

EXPERIMENTAL

Participants testing positive for human leukocyte antigen-A2 (HLA-A2) will be enrolled into one of the three Group 1 study arms. To assess the life span and decay of effector CD8+T cells, participants in group 1a will receive the 17D yellow fever vaccine and will be asked to drink deuterium (70% enriched 2H2O) labeled water for 2 weeks, on Days 0 through 14 post-vaccination.

Biological: Yellow fever vaccine; Other: Deuterium (70% enriched 2H2O) labeled water

Group 1b - Drink deuterated water on days 14 - 28 post-vaccination

EXPERIMENTAL

Participants testing positive for HLA-A2 will be enrolled into one of the three Group 1 study arms. To assess the life span and decay of effector CD8+T cells, participants in group 1b will receive the 17D yellow fever vaccine and will be asked to drink deuterium (70% enriched 2H2O) labeled water for 2 weeks, on Days 14 through 28 post-vaccination.

Biological: Yellow fever vaccine; Other: Deuterium (70% enriched 2H2O) labeled water

Group 1c - Drink deuterated water on days 0 - 28 post-vaccination

EXPERIMENTAL

Participants testing positive for HLA-A2 will be enrolled into one of the three Group 1 study arms. To assess the life span and decay of effector CD8+T cells, participants in group 1c will receive the 17D yellow fever vaccine and will be asked to drink deuterium (70% enriched 2H2O) labeled water for 4 weeks, on Days 0 through 28 post-vaccination.

Biological: Yellow fever vaccine; Other: Deuterium (70% enriched 2H2O) labeled water

Group 2a - Drink deuterated water 2 months post-vaccination

EXPERIMENTAL

To assess the homeostatic proliferation of Memory CD8 T cells, participants in group 2a will receive the 17D yellow fever vaccine and will be asked to drink deuterium (70% enriched 2H2O) labeled water 2 months post-vaccination.

Biological: Yellow fever vaccine; Other: Deuterium (70% enriched 2H2O) labeled water

Group 2b - Drink deuterated water 6 months post-vaccination

EXPERIMENTAL

To assess the homeostatic proliferation of Memory CD8 T cells, participants in group 2b will receive the 17D yellow fever vaccine and will be asked to drink deuterium (70% enriched 2H2O) labeled water 6 months post-vaccination.

Biological: Yellow fever vaccine; Other: Deuterium (70% enriched 2H2O) labeled water

Group 3 - Drink deuterated water for up to 8 weeks without vaccination

EXPERIMENTAL

To assess homeostatic turnover of CD8+ T lymphocytes in general, unvaccinated participants will be asked to drink deuterium (70% enriched 2H2O) labeled water for up to 8 weeks.

Other: Deuterium (70% enriched 2H2O) labeled water

Group 4a - Drink deuterated water on days 0 - 7 post-vaccination, with fine needle aspirate

EXPERIMENTAL

To assess homeostatic turnover of monocytes participants in group 4a will receive the 17D yellow fever vaccine and will be asked to drink deuterium (70% enriched 2H2O) labeled water on Days 0 through 7 post-vaccination. Participants will undergo two fine needle aspirate (FNA) procedures to examine the immune response in the lymph nodes.

Biological: Yellow fever vaccine; Other: Deuterium (70% enriched 2H2O) labeled water

Group 4b - Drink deuterated water for 7 days without vaccination

EXPERIMENTAL

To assess homeostatic turnover of monocytes participants in group 4b, unvaccinated participants will will be asked to drink deuterium (70% enriched 2H2O) labeled water for 7 days post enrollment.

Other: Deuterium (70% enriched 2H2O) labeled water

Interventions

Yellow fever vaccine BIOLOGICAL

The yellow fever vaccine (YFV-17D) 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 (IDS) between 2 to 8 degrees Celsius as per the manufacturer's instructions. It will be transported to the Hope Clinic per the Standard Operating Procedures.

Also known as: YF-VAX®

Group 1a - Drink deuterated water on days 0 - 14 post-vaccination; Group 1b - Drink deuterated water on days 14 - 28 post-vaccination; Group 1c - Drink deuterated water on days 0 - 28 post-vaccination; Group 2a - Drink deuterated water 2 months post-vaccination; Group 2b - Drink deuterated water 6 months post-vaccination; Group 4a - Drink deuterated water on days 0 - 7 post-vaccination, with fine needle aspirate

Deuterium (70% enriched 2H2O) labeled water OTHER

70% enriched 2H2O will be obtained from Cambridge Isotope Laboratories (Andover, MA) in sterile 1 Liter containers. An Emory Investigational Drug Service (IDS) pharmacist will prepare sterile 50 milliliter aliquots with a tamper seal which will be transported to the Hope Clinic at room temperature.

Also known as: D20, deuterated water, 2H2O

Group 1a - Drink deuterated water on days 0 - 14 post-vaccination; Group 1b - Drink deuterated water on days 14 - 28 post-vaccination; Group 1c - Drink deuterated water on days 0 - 28 post-vaccination; Group 2a - Drink deuterated water 2 months post-vaccination; Group 2b - Drink deuterated water 6 months post-vaccination; Group 3 - Drink deuterated water for up to 8 weeks without vaccination; Group 4a - Drink deuterated water on days 0 - 7 post-vaccination, with fine needle aspirate; Group 4b - Drink deuterated water for 7 days without vaccination

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Able to understand and give informed consent
• Age 18-45 years
• Participant agrees not to take any live vaccines 30 days before or after (14 days for inactivated, including coronavirus disease 2019 (COVID-19) vaccination) yellow fever vaccination (not applicable to Group 3 and 4b participants)
• Participant agrees to not receive any other vaccination during the 2H2O labeling period
• Women of child bearing potential must agree to use effective birth control for the entire duration of the study. A negative urine pregnancy test must be documented prior to vaccination or 2H2O intake. Participants who have a history of surgical sterilization or post-menopausal status \>1 year, are not required to have a pregnancy test.
• Positive for the HLA-A2 allele (not applicable to Group 3 or 4 participants)

You may not qualify if:

• Prior receipt of a yellow fever vaccine (not applicable for Group 2 participants)
• Lived in a country/area which is endemic for yellow fever (not applicable to Group 2 participants)
• Travel to country/area which is endemic for yellow fever. Subject to investigator discretion
• History of previous West Nile, Dengue, St. Louis encephalitis, Japanese encephalitis vaccination or infection
• Any history of allergy to eggs, chicken or gelatin or to any previous vaccine (not applicable to Group 2 (if received YFV-17D outside of study), 3 and 4b participants)
• 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.
• History of HIV infection
• Active Hepatitis B or Hepatitis C infection
• COVID-19 infection within 30 days prior to enrollment. Symptoms of COVID-19 must be completely resolved before enrollment.
• 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.
• 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
• Thymus gland problems (such as myasthenia gravis, DiGeorge syndrome, thymoma) or removal of thymus gland or history of autoimmune disorder
• History of neurological or neurodegenerative disorders (ex, Guillain-Barré, peripheral neuropathy, epilepsy, etc.). Subject to investigator assessment and discretion.
• Receipt of a blood products or immune globulin product within 42 days of enrollment. Participants who received COVID monoclonal antibodies (mAbs) for treatment are not excluded.
• Pregnant women and nursing mothers or women who are planning to become pregnant for the duration of the study.

Sponsors & Collaborators

• Sri Edupuganti: lead
• University of California, Berkeley: collaborator
• National Institutes of Health (NIH): collaborator
• National Institute of Allergy and Infectious Diseases (NIAID): collaborator

Study Sites (1)

The Hope Clinic of Emory Vaccine Center

Decatur, Georgia, 30030, United States

Location

MeSH Terms

Conditions

Yellow Fever

Interventions

Yellow Fever Vaccine; Deuterium

Condition Hierarchy (Ancestors)

Mosquito-Borne Diseases; Vector Borne Diseases; Infections; Arbovirus Infections; Virus Diseases; Flavivirus Infections; Flaviviridae Infections; RNA Virus Infections; Hemorrhagic Fevers, Viral

Intervention Hierarchy (Ancestors)

Viral Vaccines; Vaccines; Biological Products; Complex Mixtures; Hydrogen; Elements; Inorganic Chemicals; Gases; Isotopes

Study Officials

• Sri Edupuganti, MD

  Emory University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: February 3, 2011
• First Posted: February 4, 2011
• Study Start: April 15, 2019
• Primary Completion: October 25, 2024
• Study Completion: October 25, 2024
• Last Updated: April 29, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)