Yellow Fever Vaccine Immune Response Study

Overseen By Srilatha Edupuganti, MD, MPH

Age: 18 - 65

Sex: Any

Trial Phase: Phase 4

Sponsor: Emory University

Must not be taking: Immunosuppressants, Antineoplastics

Disqualifiers: Yellow fever vaccine, Impaired immunity, HIV, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 4

74 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you are on immunosuppressive medications or have certain medical conditions, you may not be eligible to participate.

What data supports the effectiveness of the yellow fever vaccine treatment?

The yellow fever vaccines, including YF-Vax and Stamaril, have been shown to be highly effective, with studies reporting seroconversion rates (development of detectable antibodies in the blood) of 94.44% to 100% after vaccination. These vaccines are also considered safe, with low rates of severe adverse reactions, supporting their use in preventing yellow fever in endemic areas. ^{1 2 3 4 5}

Is the yellow fever vaccine generally safe for humans?

The yellow fever vaccine, including versions like Stamaril and YF-Vax, is generally considered safe for humans. Studies show that serious adverse events are rare, and most reactions are mild or moderate. However, certain groups, such as the elderly, may have a higher risk of adverse effects. ^{1 3 4 6 7}

How is the Yellow Fever Virus Vaccine different from other treatments for yellow fever?

The Yellow Fever Virus Vaccine, specifically the YF-17D strain, is unique because it is a live-attenuated vaccine, meaning it uses a weakened form of the virus to trigger a strong and long-lasting immune response, including lifelong neutralizing antibodies and a robust T cell response, unlike most other vaccines. ^{1 2 4 8 9}

Research Team

Rafi Ahmed, PhD

Principal Investigator

Emory University

Sri Edupuganti, MD, MPH

Principal Investigator

Emory University

Eligibility Criteria

This trial is for healthy adults aged 18-45 who haven't lived in yellow fever areas or had certain viral infections/vaccinations. Participants must not be pregnant, plan to become pregnant, or have immune system issues. They should avoid other vaccines and some medications before and after getting the yellow fever vaccine.

Inclusion Criteria

I understand the study and agree to participate.

I agree not to take live vaccines around the time of my trial participation.

I am using birth control and can provide a negative pregnancy test, or I am not able to become pregnant due to surgery or menopause.

Exclusion Criteria

Prior receipt of a yellow fever vaccine

Any condition in the opinion of the investigator that would interfere with the proper conduct of the trial

I have not received blood products or immune globulin within the last 42 days.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Vaccination

Participants receive the Yellow Fever Vaccine on Day 0 at the FDA-approved dose and route of administration

1 day

1 visit (in-person)

Post-vaccination Monitoring

Participants undergo post-vaccination blood draws and other procedures based on arm assignment

360 days

Multiple visits on Day 3, Day 7, Day 14, Day 21, Day 28, Day 90, Day 180, Day 360

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Yellow Fever Virus Vaccine

Trial Overview The study tests how the human body responds to the YFV-17D (YF-VAX) yellow fever vaccine. It's a live attenuated virus used as a model for studying immune reactions to viruses over one month to one year.

Participant Groups

Group I: HLA-A202-: Yellow Fever Vaccine and Post-vaccination Blood Draws Experimental Treatment 1 Intervention

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

Group II: HLA-A202+: Yellow Fever Vaccine, Post-vaccination Blood Draws and Leukapheresis Experimental Treatment 1 Intervention

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

Group III: HLA-A202+: Yellow Fever Vaccine, Post-vaccination Blood Draws and Fine Needle Aspirate Experimental Treatment 1 Intervention

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

Group IV: HLA-A202+: Yellow Fever Vaccine and Post-vaccination Blood Draws Experimental Treatment 1 Intervention

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

Yellow Fever Virus Vaccine is already approved in United States, European Union for the following indications:

Approved in United States as YF-Vax for:

• Yellow Fever Prophylaxis

Approved in European Union as Stamaril for:

• Yellow Fever Prophylaxis

Who Is Running the Clinical Trial?

Emory University

Lead Sponsor

Trials

1,735

Recruited

2,605,000+

National Institute of Allergy and Infectious Diseases (NIAID)

Collaborator

Trials

3,361

Recruited

5,516,000+

National Institutes of Health (NIH)

Collaborator

Trials

2,896

Recruited

8,053,000+

Findings from Research

A total of 627,079 individuals received the STAMARIL vaccine from May 2017 to June 2021, with only 0.2% reporting adverse events, indicating a strong safety profile for this alternative yellow fever vaccine during a supply shortage.

Serious adverse events were rare, with only seven cases of neurotropic disease and three cases of viscerotropic disease reported, supporting the conclusion that STAMARIL is a safe and effective option for yellow fever vaccination.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enhanced safety surveillance of STAMARIL® yellow fever vaccine provided under the expanded access investigational new drug program in the USA. Rojas, A., Hachey, W., Kaur, G., et al.[2023]

The study involving 60 healthy adults demonstrated that the new Yellow Fever vaccine (SII YFV) is safe and immunogenic, with no serious adverse events reported and a high seroconversion rate of 94.44% for subcutaneous and 100% for both intramuscular and STAMARIL® groups.

Solicited reactions were relatively low, with 10% for SII YFV SC, 40% for SII YFV IM, and 25% for STAMARIL®, indicating that the new vaccine has a favorable safety profile compared to existing options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase I clinical study to assess safety and immunogenicity of yellow fever vaccine. Desai, S., Anil, K., Potey, AV., et al.[2022]

In a study of 2,514 participants, both yellow fever vaccines, Stamaril and Vacina Contra Febre Amarela (VCFA), demonstrated similar safety profiles, with only 2.2% of subjects reporting severe adverse reactions.

The vaccines were well-tolerated, with no immediate reactions observed and only one serious adverse event linked to vaccination, supporting their use for routine immunization against yellow fever in endemic regions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of two yellow fever vaccines for routine immunization programs in Argentina. Ripoll, C., Ponce, A., Wilson, MM., et al.[2019]

In a study involving 211 healthy adults, the new yellow fever vaccine (PM-YF) demonstrated higher immune response levels shortly after vaccination compared to the commercially available vaccine (Arilvax), but both provided equivalent protection one month later (100% vs 99% seroprotection).

Both vaccines were found to be safe, with no serious adverse reactions or significant liver function abnormalities reported, indicating that they are both effective and well-tolerated options for yellow fever vaccination.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of the immunogenicity and safety of two 17D yellow fever vaccines. Lang, J., Zuckerman, J., Clarke, P., et al.[2019]

The yellow fever vaccine (YFV) was found to be safe and well tolerated in HIV-infected patients with high CD4 T-cell counts, showing that it can be administered without significant risk, as evidenced by a study involving 40 HIV+ individuals and 31 HIV- individuals.

While both groups developed protective antibody levels after vaccination, HIV+ patients exhibited a lower T-cell response compared to HIV- participants, indicating that while the vaccine is effective, the immune response may be less robust in those with HIV.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunogenicity and safety of yellow fever vaccine in HIV-1-infected patients. Colin de Verdiere, N., Durier, C., Samri, A., et al.[2019]

The review of 276 million doses of Stamaril® vaccine shows a favorable safety profile, particularly regarding serious adverse events, which are reported at lower rates than previously estimated for yellow fever vaccines.

The findings provide valuable insights for healthcare providers, confirming that Stamaril's safety is consistent with its product characteristics, especially for at-risk groups like the elderly, pregnant women, and immunosuppressed individuals.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety profile of the yellow fever vaccine Stamaril®: a 17-year review. Cottin, P., Niedrig, M., Domingo, C.[2013]

Elderly individuals (ages 60-81) showed a delayed immune response to the yellow fever vaccine (YF-17D), with only 50% achieving seroprotection by day 10 compared to 77% of younger participants (ages 18-28).

Higher levels of viraemia were observed in the elderly, with 86% showing detectable YF-17D RNA, suggesting that a weaker immune response may increase the risk of serious adverse events following vaccination.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Elderly subjects have a delayed antibody response and prolonged viraemia following yellow fever vaccination: a prospective controlled cohort study. Roukens, AH., Soonawala, D., Joosten, SA., et al.[2022]

Both the YF-17D-213/77 and YF-17DD yellow fever vaccine substrains effectively triggered a balanced immune response in children, with slight differences in cytokine profiles, indicating their potential for universal use in immunization.

Revaccination with YF-17DD improved the immune response in previously non-seroconverting children, highlighting its efficacy in enhancing immunity regardless of initial antibody levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

17DD and 17D-213/77 yellow fever substrains trigger a balanced cytokine profile in primary vaccinated children. Campi-Azevedo, AC., de Araújo-Porto, LP., Luiza-Silva, M., et al.[2021]

The live-attenuated Yellow Fever virus vaccine (YF-17D) has been administered to over 600 million people and induces long-lasting neutralizing antibodies and a strong T cell response, similar to responses seen in acute infections.

Research over the past few decades has revealed that YF vaccination provides valuable insights into human immune responses, making it a key model for understanding how to achieve optimal immunity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Yellow fever virus vaccination: an emblematic model to elucidate robust human immune responses. Bovay, A., Fuertes Marraco, SA., Speiser, DE.[2021]

References

1. England pubmed.ncbi.nlm.nih.gov

Enhanced safety surveillance of STAMARIL® yellow fever vaccine provided under the expanded access investigational new drug program in the USA. [2023]

2. England pubmed.ncbi.nlm.nih.gov

A phase I clinical study to assess safety and immunogenicity of yellow fever vaccine. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

Evaluation of two yellow fever vaccines for routine immunization programs in Argentina. [2019]

4. United States pubmed.ncbi.nlm.nih.gov

Comparison of the immunogenicity and safety of two 17D yellow fever vaccines. [2019]

5. England pubmed.ncbi.nlm.nih.gov

Immunogenicity and safety of yellow fever vaccine in HIV-1-infected patients. [2019]

6. England pubmed.ncbi.nlm.nih.gov

Safety profile of the yellow fever vaccine Stamaril®: a 17-year review. [2013]

7. United States pubmed.ncbi.nlm.nih.gov

Elderly subjects have a delayed antibody response and prolonged viraemia following yellow fever vaccination: a prospective controlled cohort study. [2022]

8. United States pubmed.ncbi.nlm.nih.gov

17DD and 17D-213/77 yellow fever substrains trigger a balanced cytokine profile in primary vaccinated children. [2021]

9. United States pubmed.ncbi.nlm.nih.gov

Yellow fever virus vaccination: an emblematic model to elucidate robust human immune responses. [2021]