Yellow FeverPhase 4NCT00694655
Human Immune Responses to Yellow Fever Vaccination
A Phase 4 study testing Yellow Fever Vaccine, Leukapheresis and Fine-needle aspiration (FNA) in people with Yellow Fever, run by Emory University at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 45 yearsHealthy volunteers can take part
- Conditions the study is for
- Yellow Fever
- What is being tested?
- Yellow Fever Vaccine, Leukapheresis and Fine-needle aspiration (FNA)
- Type of treatment
- Vaccines, Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 239 participants
- Where
- 1 siteUnited States
- Study dates
- May 2008to 29 Aug 2024
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 45 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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.
Who cannot join
- 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
Show all 15Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
The Hope Clinic of the Emory Vaccine Center
Decatur, Georgia, 30030
About this study
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.
Read the detailed description
Yellow fever (YF) 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.
- Conditions
- Yellow Fever
- Being tested
- Yellow Fever Vaccine, Leukapheresis, Fine-needle aspiration (FNA)
- Keywords
- Yellow fever, Vaccine, Immunity, Yellow fever vaccine, CD8 T cell responses
- Medical subject headings
- Yellow Fever
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Yellow Fever VaccineBiological
Also called YF-VAX, YFV-17D Yellow Fever Vaccine
Participants receive Yellow Fever Vaccine, at the FDA approved dose and route of administration.
LeukapheresisProcedure or surgery
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.
Fine-needle aspiration (FNA)Procedure or surgery
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.
| Study group | Role | What they receive |
|---|---|---|
| Arm A: Yellow Fever Vaccine in HLA-A202+ Participants | Experimental | HLA-A202+ participants receiving the Yellow Fever Vaccine plus post-vaccination blood draws. Receives: 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. Receives: 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. Receives: 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. Receives: Biological: Yellow Fever Vaccine |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: Day 14, Day 21, Day 28, Day 90, Day 180, Day 360
Secondary outcomes (2)
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.
Measured: Day 0 (day of vaccination), Day 21, Day 180
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.
Measured: Day 0 (day of vaccination), Day 21, Day 180
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Jun 2008 (estimated)
- Study startMay 2008
- Primary completion29 Aug 2024
- Study completion29 Aug 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Yellow FeverStudies of the same condition, open and under way.
- More trials run by Emory UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 239 participants (actual)
Sponsor and investigators
- Lead sponsor
- Emory University
- Sponsor type
- University, hospital or other
- Collaborators
- National Institutes of Health (NIH), National Institute of Allergy and Infectious Diseases (NIAID)
- Responsible party
- Principal investigator, Sri Edupuganti, Emory University
- Investigators
- Rafi Ahmed, PhD, Study chair, Emory UniversitySri Edupuganti, MD, MPH, Principal investigator, Emory University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00694655
- Sponsor's protocol ID
- IRB00009560
- Other IDs
- U19AI057266
- Status last verified
- Sep 2025
- First submitted
- 19 May 2008
- Last updated
- 3 Oct 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 19933869
Study at a glance
From the registry record, last updated by the sponsor on 3 Oct 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Human Immune Responses to Yellow Fever Vaccination
- ClinicalTrials.gov ID
- NCT00694655
- Acronym / sponsor ID
- IRB00009560
- Conditions
- Yellow Fever
- Keywords
- Yellow fever, Vaccine, Immunity, Yellow fever vaccine, CD8 T cell responses
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 239 participants (actual)
- Lead sponsor
- Emory UniversityUniversity, hospital or other
- Collaborators
- National Institutes of Health (NIH), National Institute of Allergy and Infectious Diseases (NIAID)
- Study start
- May 2008 (actual)
- Primary completion
- 29 Aug 2024 (actual)
- Study completion
- 29 Aug 2024 (actual)
- First posted
- 10 Jun 2008 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Yellow fever (YF) 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 design
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Arm A: Yellow Fever Vaccine in HLA-A202+ Participants | Experimental | Biological: Yellow Fever VaccineHLA-A202+ participants receiving the Yellow Fever Vaccine plus post-vaccination blood draws. |
| Arm B: Yellow Fever Vaccine and Leukapheresis in HLA-A202+ Participants | Experimental | Biological: Yellow Fever Vaccine, Procedure: LeukapheresisHLA-A202+ participants receiving the Yellow Fever Vaccine plus post-vaccination blood draws and leukapheresis. |
| Arm C: Yellow Fever Vaccine and Fine Needle Aspirate in HLA-A202+ Participants | Experimental | Biological: Yellow Fever Vaccine, Procedure: Fine-needle aspiration (FNA)HLA-A202+ participants receiving the Yellow Fever Vaccine plus post-vaccination blood draws and fine needle aspirate. |
| Arm D: Yellow Fever Vaccine in HLA-A202- Participants | Experimental | Biological: Yellow Fever VaccineHLA-A202- participants receiving the Yellow Fever Vaccine plus post-vaccination blood draws. |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (4 listed)
- 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.
Key exclusion criteria (15 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Yellow Fever VaccineAlso: YF-VAX, YFV-17D Yellow Fever VaccineParticipants receive Yellow Fever Vaccine, at the FDA approved dose and route of administration. | Biological | 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 |
| LeukapheresisIn 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. | Procedure or surgery | Arm B: Yellow Fever Vaccine and Leukapheresis in HLA-A202+ Participants |
| Fine-needle aspiration (FNA)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. | Procedure or surgery | Arm C: Yellow Fever Vaccine and Fine Needle Aspirate in HLA-A202+ Participants |
Primary outcome
Magnitude of Yellow Fever Virus (YFV) specific T Cell Responses
Time frame: Day 0 (day of vaccination), Day 7, Day 14, Day 21, Day 28, Day 90, Day 180, Day 360
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.
Quality of YFV-specific T Cell Responses
Time frame: Day 14, Day 21, Day 28, Day 90, Day 180, Day 360
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.
2 secondary outcomes
Characterization of Cytomegalovirus (CMV)
Time frame: Day 0 (day of vaccination), Day 21, Day 180
Phenotypic Analysis of Cytomegalovirus (CMV)
Time frame: Day 0 (day of vaccination), Day 21, Day 180
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Oct 2025.
- Results publication: PubMed 19933869Akondy 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.
- Website for the Hope Clinic of Emory Vaccine CenterLink provided by the sponsor.
- Individual participant dataSharing planned: No
Related trials for Yellow Fever
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A Phase III Control Study of the Safety and Immunogenicity of vYF in Pediatric Population
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Study on an Investigational Yellow Fever Vaccine Compared With YF-VAX in Adults in the USA
Yellow Fever, Healthy Volunteers
Recruiting
Baseline Assessment of Skin Resident Memory T Cells in Healthy Unvaccinated Participants
Yellow Fever (Healthy Volunteers), Biopsy/Methods
Active, not recruitingPhase 2
Study on an Investigational Yellow Fever Vaccine Compared With Stamaril in Adults in Europe and Asia
Yellow Fever
RecruitingObservational study
Risk Assessment of Community Spread of Multiple Endemic Infectious Diseases in a One Health Perspective
Dengue, Chikungunya
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Rafi Ahmed, PhD study chair
Emory University
Sri Edupuganti, MD, MPH principal investigator
Emory University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Yellow Fever Vaccine, Leukapheresis and Fine-needle aspiration (FNA) in people with Yellow Fever, run by Emory University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 3 Oct 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Magnitude of Yellow Fever Virus (YFV) specific T Cell Responses (time frame: Day 0 (day of vaccination), Day 7, Day 14, Day 21, Day 28, Day 90, Day 180, Day 360). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00694655, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Oct 2025; AzTrials last refreshed its copy on 6 Nov 2026.