Human Immune Responses to Yellow Fever Vaccination

The goal of this study is to use the live attenuated Yellow Fever Vaccine 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.

Study Overview

• Status: Recruiting
• Conditions: Yellow Fever
• Intervention / Treatment: Biological: Yellow Fever Vaccine

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. 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 Yellow Fever Vaccine is considered to be one of the safest and most effective viral vaccines ever developed. Yellow Fever 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 Yellow Fever Vaccine 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 Yellow Fever 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. Healthy participants will be enrolled into four study arms. Arm enrollment is determined by Human Leukocyte Antigen (HLA) type, current needs of the lab and/or willingness to participate in sampling procedures. All participants receive Yellow Fever Vaccine on Day 0 at the FDA-approved dose and route of administration. Post-vaccination procedures are determined by arm assignment. Participants will be followed for up to 360 days post-vaccination.

• Study Type: Interventional
• Enrollment (Estimated): 250
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Srilatha Edupuganti, MD, MPH; Phone Number: 404-712-1370; Email: sedupug@emory.edu

Study Locations

• United States
  • Georgia
    • Decatur, Georgia, United States, 30030
      • Recruiting
      • The Hope Clinic of the Emory Vaccine Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 43 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. Able to understand and give informed consent
2. Age 18-45 years
3. 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
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. Participants who have a history of surgical sterilization or post-menopausal status >1 year, are not required to have a pregnancy test.

Exclusion Criteria:

1. Prior receipt of a yellow fever vaccine
2. Lived in a country/area which is endemic for yellow fever
3. Travel to country/area which is endemic for yellow fever. Subject to investigator discretion
4. History of previous yellow fever, West Nile, Dengue, St. Louis encephalitis, Japanese encephalitis vaccination or infection
5. Any history of allergy to eggs, chicken or gelatin or to any previous vaccine
6. 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
7. History of HIV infection
8. Active Hepatitis B or Hepatitis C infection
9. COVID-19 infection in the last 30 days. Symptoms of COVID-19 must be completely resolved before yellow fever vaccine receipt.
10. 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
11. 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
12. Thymus gland problems (such as myasthenia gravis, DiGeorge syndrome, thymoma) or removal of thymus gland or history of autoimmune disorder
13. 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
14. Pregnant women and nursing mothers or women who are planning to become pregnant for the duration of the study
15. Any condition in the opinion of the investigator that would interfere with the proper conduct of the trial

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: HLA-A202+: Yellow Fever Vaccine and Post-vaccination Blood Draws; HLA-A202+ participants receiving Yellow Fever Vaccine plus post-vaccination blood draws.	Biological: Yellow Fever Vaccine; Participants receive Yellow Fever Vaccine, at the FDA approved dose and route of administration.; Other Names: YF-VAX; YFV-17D Yellow Fever Vaccine
Experimental: HLA-A202+: Yellow Fever Vaccine, Post-vaccination Blood Draws and Leukapheresis; HLA-A202+ participants receiving Yellow Fever Vaccine plus post-vaccination blood draws and leukapheresis.	Biological: Yellow Fever Vaccine; Participants receive Yellow Fever Vaccine, at the FDA approved dose and route of administration.; Other Names: YF-VAX; YFV-17D Yellow Fever Vaccine
Experimental: HLA-A202+: Yellow Fever Vaccine, Post-vaccination Blood Draws and Fine Needle Aspirate; HLA-A202+ participants receiving Yellow Fever Vaccine plus post-vaccination blood draws and fine needle aspirate.	Biological: Yellow Fever Vaccine; Participants receive Yellow Fever Vaccine, at the FDA approved dose and route of administration.; Other Names: YF-VAX; YFV-17D Yellow Fever Vaccine
Experimental: HLA-A202-: Yellow Fever Vaccine and Post-vaccination Blood Draws; HLA-A202- participants receiving Yellow Fever Vaccine plus post-vaccination blood draws.	Biological: Yellow Fever Vaccine; Participants receive Yellow Fever Vaccine, at the FDA approved dose and route of administration.; Other Names: YF-VAX; YFV-17D Yellow Fever Vaccine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in 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 3, Day 7, Day 14, Day 21, Day 28, Day 90, Day 180, Day 360
Change in 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 0 (day of vaccination), Day 3, Day 7, Day 14, Day 21, Day 28, Day 90, Day 180, Day 360
Change in Magnitude of YFV-specific Antibody Secreting Cells	The characterization of Yellow Fever Vaccine 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.	Day 0 (day of vaccination), Day 3, Day 7, Day 14, Day 21, Day 28, Day 90, Day 180, Day 360
Change in Quality of YFV-specific Antibody Secreting Cells	The characterization of Yellow Fever Vaccine 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.	Day 0 (day of vaccination), Day 3, Day 7, Day 14, Day 21, Day 28, Day 90, Day 180, Day 360
Change in Magnitude of YFV-specific Memory B Cells	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.	Day 0 (day of vaccination), Day 3, Day 7, Day 14, Day 21, Day 28, Day 90, Day 180, Day 360
Change in Quantity of YFV-specific Memory B Cells	The characterization of Yellow Fever Vaccine 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.	Day 0 (day of vaccination), Day 3, Day 7, Day 14, Day 21, Day 28, Day 90, Day 180, Day 360
Change in Peripheral Blood Mononuclear Cell (PBMC) Cytokines	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.	Day 0 (day of vaccination), Day 3, Day 7, Day 14, Day 21, Day 28, Day 90, Day 180, Day 360
Change in PBMC Chemokines	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.	Day 0 (day of vaccination), Day 3, Day 7, Day 14, Day 21, Day 28, Day 90, Day 180, Day 360
Change in PBMC Dendritic Cells	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.	Day 0 (day of vaccination), Day 3, Day 7, Day 14, Day 21, Day 28, Day 90, Day 180, Day 360
Change in PBMC Gene Expression	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.	Day 0 (day of vaccination), Day 3, Day 7, Day 14, Day 21, Day 28, Day 90, Day 180, Day 360

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Characterization of Epstein-Barr Virus (EBV)	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.	Day 0 (day of vaccination), Day 3, Day 7, Day 14, Day 21, Day 28, Day 90, Day 180, Day 360
Change in Phenotypic Analysis of Epstein-Barr Virus (EBV)	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.	Day 0 (day of vaccination), Day 3, Day 7, Day 14, Day 21, Day 28, Day 90, Day 180, Day 360
Change in Characterization of Cytomegalovirus (CMV)	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.	Day 0 (day of vaccination), Day 3, Day 7, Day 14, Day 21, Day 28, Day 90, Day 180, Day 360
Change in Phenotypic Analysis of Cytomegalovirus (CMV)	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.	Day 0 (day of vaccination), Day 3, Day 7, Day 14, Day 21, Day 28, Day 90, Day 180, Day 360
Change in Characterization of YFV	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.	Day 0 (day of vaccination), Day 3, Day 7, Day 14, Day 21, Day 28, Day 90, Day 180, Day 360
Change in Phenotypic Analysis of YFV	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.	Day 0 (day of vaccination), Day 3, Day 7, Day 14, Day 21, Day 28, Day 90, Day 180, Day 360

Collaborators and Investigators

• Sponsor: Emory University
• Collaborators: National Institute of Allergy and Infectious Diseases (NIAID); National Institutes of Health (NIH)
• Investigators: Study Chair: Rafi Ahmed, PhD, Emory University; Principal Investigator: Sri Edupuganti, MD, MPH, Emory University

Publications and helpful links

Helpful Links

• Website for the Hope Clinic of Emory Vaccine Center

Study record dates

Study Major Dates

• Study Start: May 1, 2008
• Primary Completion (Estimated): June 1, 2024
• Study Completion (Estimated): June 1, 2024

Study Registration Dates

• First Submitted: May 19, 2008
• First Submitted That Met QC Criteria: June 9, 2008
• First Posted (Estimated): June 10, 2008

Study Record Updates

• Last Update Posted (Actual): December 26, 2023
• Last Update Submitted That Met QC Criteria: December 20, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: Vaccine; Immunity; Yellow fever; Yellow fever vaccine; CD8 T cell responses
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Wounds and Injuries; Arbovirus Infections; Vector Borne Diseases; Flavivirus Infections; Flaviviridae Infections; Body Temperature Changes; Heat Stress Disorders; Hemorrhagic Fevers, Viral; Hyperthermia; Fever; Yellow Fever; Physiological Effects of Drugs; Immunologic Factors; Vaccines
• Other Study ID Numbers: IRB00009560; U19AI057266 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No