Human Immune Responses to Yellow Fever Vaccination

Yellow Fever Clinical Trial

Official title:

Human Immune Responses to Yellow Fever Vaccination

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT00694655
• Other study ID #: IRB00009560
• Secondary ID: U19AI057266
• Status: Recruiting
• Phase: Phase 4
• Start date: May 2008
• Est. completion date: December 31, 2025

Study information

• Verified date: April 2024
• Source: Emory University
• Contact: Srilatha Edupuganti, MD, MPH
• Phone: 404-712-1370
• Email: sedupug[@]emory.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 250
• Est. completion date: December 31, 2025
• Est. primary completion date: December 31, 2025
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 45 Years

Eligibility

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

Related Conditions & MeSH terms

• Fever
• Hyperthermia
• Yellow Fever

Intervention

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

Locations

Country	Name	City	State
United States	The Hope Clinic of the Emory Vaccine Center	Decatur	Georgia

Sponsors (3)

Lead Sponsor	Collaborator
Emory University	National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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

External Links

•   Website for the Hope Clinic of Emory Vaccine Center