Human Immune Responses to Yellow Fever Vaccination

NCT00694655 | Completed Phase 4 FDA Drug

• 2 other identifiers: IRB00009560U19AI057266
• Study Type: interventional
• Target: 239
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this study is to use the live attenuated Yellow Fever Vaccine (YFV) as a safe and effective model for viral infection to understand human immune response to viral antigens. Study participants will receive the yellow fever vaccine and participation in the study may be as short as one month or as long as one year, depending on immune responses.

Conditions

Yellow Fever

Keywords

Yellow fever; Vaccine; Immunity; Yellow fever vaccine; CD8 T cell responses

Outcome Measures

Primary Outcomes (2)

• Magnitude of Yellow Fever Virus (YFV) specific T Cell Responses

  The characterization of Yellow Fever Vaccine specific adaptive immune response will be examined as the magnitude of YFV-specific T cell responses. The schedule of follow up visits depends on if participants test positive for human leukocyte antigen (HLA) A202 and the different immune system responses that the study team is examining at the time when each participant enrolls.

  Day 0 (day of vaccination), Day 7, Day 14, Day 21, Day 28, Day 90, Day 180, Day 360

• Quality of YFV-specific T Cell Responses

  The characterization of Yellow Fever Vaccine specific adaptive immune response will be examined as the quality of YFV-specific T cell responses. The schedule of follow up visits depends on if participants test positive for HLA-A202 and the different immune system responses that the study team is examining at the time when each participant enrolls.

  Day 14, Day 21, Day 28, Day 90, Day 180, Day 360

Secondary Outcomes (2)

• Characterization of Cytomegalovirus (CMV)

  Day 0 (day of vaccination), Day 21, Day 180

• Phenotypic Analysis of Cytomegalovirus (CMV)

  Day 0 (day of vaccination), Day 21, Day 180

Other Outcomes (6)

• Magnitude of YFV-specific Antibody Secreting Cells

  Day 0 (day of vaccination), Day 3, Day 7, Day 14, Day 21, Day 28, Day 90, Day 180, Day 360

• Quality of YFV-specific Antibody Secreting Cells

  Day 0 (day of vaccination), Day 3, Day 7, Day 14, Day 21, Day 28, Day 90, Day 180, Day 360

• Magnitude of YFV-specific Memory B Cells

  Day 0 (day of vaccination), Day 3, Day 7, Day 14, Day 21, Day 28, Day 90, Day 180, Day 360

Study Arms (4)

Arm A: Yellow Fever Vaccine in HLA-A202+ Participants

EXPERIMENTAL

HLA-A202+ participants receiving the Yellow Fever Vaccine plus post-vaccination blood draws.

Biological: Yellow Fever Vaccine

Arm B: Yellow Fever Vaccine and Leukapheresis in HLA-A202+ Participants

EXPERIMENTAL

HLA-A202+ participants receiving the Yellow Fever Vaccine plus post-vaccination blood draws and leukapheresis.

Biological: Yellow Fever Vaccine; Procedure: Leukapheresis

Arm C: Yellow Fever Vaccine and Fine Needle Aspirate in HLA-A202+ Participants

EXPERIMENTAL

HLA-A202+ participants receiving the Yellow Fever Vaccine plus post-vaccination blood draws and fine needle aspirate.

Biological: Yellow Fever Vaccine; Procedure: Fine-needle aspiration (FNA)

Arm D: Yellow Fever Vaccine in HLA-A202- Participants

EXPERIMENTAL

HLA-A202- participants receiving the Yellow Fever Vaccine plus post-vaccination blood draws.

Biological: Yellow Fever Vaccine

Interventions

Yellow Fever Vaccine BIOLOGICAL

Participants receive Yellow Fever Vaccine, at the FDA approved dose and route of administration.

Also known as: YF-VAX, YFV-17D Yellow Fever Vaccine

Arm A: Yellow Fever Vaccine in HLA-A202+ Participants; Arm B: Yellow Fever Vaccine and Leukapheresis in HLA-A202+ Participants; Arm C: Yellow Fever Vaccine and Fine Needle Aspirate in HLA-A202+ Participants; Arm D: Yellow Fever Vaccine in HLA-A202- Participants

Leukapheresis PROCEDURE

In leukapheresis blood is drawn and then the white blood cells are separated from the blood sample in a laboratory procedure. Once the white blood cells are returned the blood is returned back to the bloodstream of the participant who provided the sample.

Arm B: Yellow Fever Vaccine and Leukapheresis in HLA-A202+ Participants

Fine-needle aspiration (FNA) PROCEDURE

In fine-needle aspiration a cell sample is collected using a needle and syringe. Fine-needle aspiration is typically used as a minimally invasive method of sample collection used to confirm a diagnosis.

Arm C: Yellow Fever Vaccine and Fine Needle Aspirate in HLA-A202+ Participants

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
• Women of child bearing potential must agree to use effective birth control throughout the duration of the study. A negative urine pregnancy test must be documented prior to vaccination. Participants who have a history of surgical sterilization or post-menopausal status \>1 year, are not required to have a pregnancy test.

You may not qualify if:

• Prior receipt of a yellow fever vaccine
• Lived in a country/area which is endemic for yellow fever
• Travel to country/area which is endemic for yellow fever. Subject to investigator discretion
• History of previous yellow fever, 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
• 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 in the last 30 days. Symptoms of COVID-19 must be completely resolved before yellow fever vaccine receipt.
• 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
• Recipient of a blood products or immune globulin product within 42 days of the vaccination visit. 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
• Any condition in the opinion of the investigator that would interfere with the proper conduct of the trial

Sponsors & Collaborators

• Emory University: lead
• National Institutes of Health (NIH): collaborator
• National Institute of Allergy and Infectious Diseases (NIAID): collaborator

Study Sites (1)

The Hope Clinic of the Emory Vaccine Center

Decatur, Georgia, 30030, United States

Location

Related Publications (1)

• Akondy RS, Monson ND, Miller JD, Edupuganti S, Teuwen D, Wu H, Quyyumi F, Garg S, Altman JD, Del Rio C, Keyserling HL, Ploss A, Rice CM, Orenstein WA, Mulligan MJ, Ahmed R. The yellow fever virus vaccine induces a broad and polyfunctional human memory CD8+ T cell response. J Immunol. 2009 Dec 15;183(12):7919-30. doi: 10.4049/jimmunol.0803903.

  PMID: 19933869 RESULT

Related Links

• Website for the Hope Clinic of Emory Vaccine Center

MeSH Terms

Conditions

Yellow Fever

Interventions

Yellow Fever Vaccine; Leukapheresis; Biopsy, Fine-Needle

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; Cytapheresis; Biological Therapy; Therapeutics; Blood Component Removal; Leukocyte Reduction Procedures; Cell Separation; Cytological Techniques; Clinical Laboratory Techniques; Investigative Techniques; Biopsy, Needle; Biopsy; Cytodiagnosis; Diagnostic Techniques and Procedures; Diagnosis; Specimen Handling; Diagnostic Techniques, Surgical; Surgical Procedures, Operative; Punctures

Study Officials

• Rafi Ahmed, PhD

  Emory University

  STUDY CHAIR

• Sri Edupuganti, MD, MPH

  Emory University

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: May 19, 2008
• First Posted: June 10, 2008
• Study Start: May 1, 2008
• Primary Completion: August 29, 2024
• Study Completion: August 29, 2024
• Last Updated: October 3, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)