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Human Immune Responses to Yellow Fever Vaccination

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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00694655
Recruitment Status : Recruiting
First Posted : June 10, 2008
Last Update Posted : December 2, 2022
Sponsor:
Collaborators:
National Institutes of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Information provided by (Responsible Party):
Sri Edupuganti, Emory University

Study Description
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Brief Summary:
The goal of this study is to use the live attenuated yellow fever vaccine, YFV-17D (YF-VAX®, Sanofi-Pasteur) 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.

Condition or disease Intervention/treatment Phase
Yellow Fever Biological: Yellow Fever Virus Vaccine Phase 4

Detailed Description:

Yellow fever is a viral disease that is transmitted to humans through the bite of an infected mosquito. Yellow fever is a life-threatening infection that can result in hepatitis, renal failure and coagulation abnormalities, and in severe cases, death. Yellow fever was a major public health threat in the colonial United States in the 18th and 19th centuries.

Yellow fever is endemic in over 40 countries, and approximately 125 countries require proof of vaccination for entry by travelers at risk. An estimated 200,000 cases of yellow fever occur annually in South America and Africa, making it an important vaccine-preventable disease among travelers to endemic areas. Yellow fever can be prevented by vaccination with the yellow fever vaccine (YFV-17D). Currently, the Centers for Disease Control and Prevention (CDC) and the World Health Organization (WHO) recommend yellow fever vaccination for persons ≥ 9 months of age who are traveling to or living in a yellow fever endemic area.

The YFV-17D vaccine is considered to be one of the safest and most effective viral vaccines ever developed. YFV-17D vaccine is known to stimulate broad-spectrum immune responses, including cytotoxic T cells, and Th1 and Th2 responses, as well as neutralizing antibody titers that can persist for up to 30 years, after a single vaccination. Despite the great success of this empiric vaccine, there has been relatively little understanding of the mechanisms by which YFV-17D induces such robust protective immune responses. The researchers hope to apply the best contemporary methods in immunology, genomics, and proteomics to characterize in detail a successful immune response to YFV-17D vaccination. This characterization should identify new immunologic predictors that could serve as surrogates for future vaccine efficacy studies. In addition, these findings could guide development of a safer yellow fever vaccine (or the derivation of safer alternative vaccination regimens using the currently available vaccine).

This study plans to recruit both travelers to yellow fever endemic areas as well as non-travelers for participation. Participants will be followed for up to 360 days post-vaccination.

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 200 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Official Title: Human Immune Responses to Yellow Fever Vaccination
Study Start Date : May 2008
Estimated Primary Completion Date : December 2025
Estimated Study Completion Date : December 2025

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Yellow Fever Virus Vaccine
Participants receiving the yellow fever virus vaccine
 Biological: Yellow Fever Virus Vaccine
Participants will receive the FDA-approved YFV-17D vaccine, at the FDA approved dose and route of administration.
Other Names:
  • YF-VAX
  • YFV-17D Yellow Fever Vaccine


Outcome Measures
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Primary Outcome Measures :
  1. Change in Magnitude of YFV-specific T Cell Responses [ Time Frame: Day 0 (day of vaccination), Day 14, Day 21, Day 28, Day 90, Day 180, Day 360 ]
    The characterization of yellow fever vaccine (YFV-17D) 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.

  2. Change in Quality of YFV-specific T Cell Responses [ Time Frame: Day 0 (day of vaccination), Day 14, Day 21, Day 28, Day 90, Day 180, Day 360 ]
    The characterization of yellow fever vaccine (YFV-17D) 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.

  3. Change in Magnitude of YFV-specific Antibody Secreting Cells [ Time Frame: Day 0 (day of vaccination), Day 14, Day 21, Day 28, Day 90, Day 180, Day 360 ]
    The characterization of yellow fever vaccine (YFV-17D) specific adaptive immune response will be examined as the magnitude of YFV-specific antibody secreting cells. 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.

  4. Change in Quality of YFV-specific Antibody Secreting Cells [ Time Frame: Day 0 (day of vaccination), Day 14, Day 21, Day 28, Day 90, Day 180, Day 360 ]
    The characterization of yellow fever vaccine (YFV-17D) specific adaptive immune response will be examined as the quality of YFV-specific antibody secreting cells. 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.

  5. Change in Magnitude of YFV-specific Memory B Cells [ Time Frame: Day 0 (day of vaccination), Day 14, Day 21, Day 28, Day 90, Day 180, Day 360 ]
    The characterization of yellow fever vaccine (YFV-17D) specific adaptive immune response will be examined as the magnitude of YFV-specific memory B cells. 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.

  6. Change in Quantity of YFV-specific Memory B Cells [ Time Frame: Day 0 (day of vaccination), Day 14, Day 21, Day 28, Day 90, Day 180, Day 360 ]
    The characterization of yellow fever vaccine (YFV-17D) specific adaptive immune response will be examined as the quantity of YFV-specific memory B cells. 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.

  7. Change in Peripheral Blood Mononuclear Cell (PBMC) Cytokines [ Time Frame: Day 0 (day of vaccination), Day 14, Day 21, Day 28, Day 90, Day 180, Day 360 ]
    To determine the signatures of innate immune responses, cytokines on peripheral blood mononuclear cells (PBMCs) will be examined. 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.

  8. Change in PBMC Chemokines [ Time Frame: Day 0 (day of vaccination), Day 14, Day 21, Day 28, Day 90, Day 180, Day 360 ]
    To determine the signatures of innate immune responses, chemokines on PBMCs will be examined. 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.

  9. Change in PBMC Dendritic Cells [ Time Frame: Day 0 (day of vaccination), Day 14, Day 21, Day 28, Day 90, Day 180, Day 360 ]
    To determine the signatures of innate immune responses, dendritic cells on PBMCs will be examined. 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.

  10. Change in PBMC Gene Expression [ Time Frame: Day 0 (day of vaccination), Day 14, Day 21, Day 28, Day 90, Day 180, Day 360 ]
    To determine the signatures of innate immune responses, microarray analyses for gene expression on PBMCs will be performed. 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.


Secondary Outcome Measures :
  1. Change in Characterization of Epstein-Barr Virus (EBV) [ Time Frame: Day 0 (day of vaccination), Day 14, Day 21, Day 28, Day 90, Day 180, Day 360 ]
    Characterization of EBV cluster of differentiation 8 (CD8) T cells will be performed. 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.

  2. Change in Phenotypic Analysis of Epstein-Barr Virus (EBV) [ Time Frame: Day 0 (day of vaccination), Day 14, Day 21, Day 28, Day 90, Day 180, Day 360 ]
    Phenotypic analysis of EBV CD8 T cells will be performed. 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.

  3. Change in Characterization of Cytomegalovirus (CMV) [ Time Frame: Day 0 (day of vaccination), Day 14, Day 21, Day 28, Day 90, Day 180, Day 360 ]
    Characterization of CMV CD8 T cells will be performed. 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.

  4. Change in Phenotypic Analysis of Cytomegalovirus (CMV) [ Time Frame: Day 0 (day of vaccination), Day 14, Day 21, Day 28, Day 90, Day 180, Day 360 ]
    Phenotypic analysis of CMV CD8 T cells will be performed. 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.

  5. Change in Characterization of YFV [ Time Frame: Day 0 (day of vaccination), Day 14, Day 21, Day 28, Day 90, Day 180, Day 360 ]
    Characterization of YFV CD8 T cells will be performed. 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.

  6. Change in Phenotypic Analysis of YFV [ Time Frame: Day 0 (day of vaccination), Day 14, Day 21, Day 28, Day 90, Day 180, Day 360 ]
    Phenotypic analysis of YFV CD8 T cells will be performed. 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.


Eligibility Criteria
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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. If possible, participants agree not to take any vaccines within 30 days before or 30 days after yellow fever vaccination
  4. 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.

Exclusion Criteria:

  1. 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 for the study duration
  11. Any condition in the opinion of the investigator that would interfere with the proper conduct of the trial
  12. Received the second coronavirus disease 2019 (COVID-19) vaccine less than 21 days before receiving the Yellow Fever Vaccine.
  13. COVID-19 infection in the last 60 days. Symptoms of COVID-19 symptoms must be completely resolved before yellow fever vaccine receipt.
Contacts and Locations
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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): NCT00694655


Contacts
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Contact: Srilatha Edupuganti, MD, MPH 404-712-1370 sedupug@emory.edu

Locations
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United States, Georgia
The Hope Clinic of the Emory Vaccine Center Recruiting
Decatur, Georgia, United States, 30030
Sponsors and Collaborators
Emory University
National Institutes of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Investigators
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Study Chair: Rafi Ahmed, PhD Emory University
Principal Investigator: Sri Edupuganti, MD, MPH Emory University
More Information
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Additional Information:

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Responsible Party: Sri Edupuganti, Professor, Emory University
ClinicalTrials.gov Identifier: NCT00694655    
Other Study ID Numbers: IRB00009560
5U19AI057266 ( U.S. NIH Grant/Contract )
First Posted: June 10, 2008    Key Record Dates
Last Update Posted: December 2, 2022
Last Verified: November 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Sri Edupuganti, Emory University:
Yellow fever
Vaccine
Immunity
Yellow fever vaccine
CD8 T cell responses
Additional relevant MeSH terms:
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Yellow Fever
Fever
Hyperthermia
Body Temperature Changes
Heat Stress Disorders
Wounds and Injuries
Arbovirus Infections
Vector Borne Diseases
Infections
 Virus Diseases
Flavivirus Infections
Flaviviridae Infections
RNA Virus Infections
Hemorrhagic Fevers, Viral
Vaccines
Immunologic Factors
Physiological Effects of Drugs