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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines how the immune system responds to the yellow fever vaccine, which serves as a model for understanding the body's reaction to viruses. Participants will receive the yellow fever vaccine and may be involved for as short as one month or as long as one year, depending on their immune response. The study includes different groups, some involving additional procedures like blood draws or other tests. Those who have never received a yellow fever vaccine and have not lived in or traveled to areas where the disease is common might be a good fit. As a Phase 4 trial, this research aims to understand how the already FDA-approved and effective vaccine benefits more patients.

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 is the safety track record for the Yellow Fever Virus Vaccine?

Research shows that the yellow fever vaccine is generally safe and has been used for many years to protect against yellow fever, a serious viral infection. Studies have found that the vaccine triggers a strong immune response, helping the body effectively fight off the virus.

Most people experience only mild side effects, such as soreness at the injection site or a mild fever. Serious side effects are rare. Research also indicates that the immune response from the yellow fever vaccine is strong and long-lasting, providing protection for a lifetime.

Since this trial is in a late phase, substantial evidence already supports the vaccine's safety. The FDA has approved the vaccine, confirming it has passed many safety tests. Those considering joining a clinical trial should discuss any concerns with their healthcare provider. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about the Yellow Fever Vaccine Immune Response Study because it explores how the immune system reacts to the vaccine in different ways. Unlike standard yellow fever vaccines, this trial examines the vaccine's effects on participants with a specific genetic marker, HLA-A202, which might provide insights into personalized responses to vaccination. Additionally, some arms of the trial involve innovative methods like leukapheresis and fine needle aspiration, which help researchers gather detailed information about immune cells and their activity post-vaccination. This approach could lead to breakthroughs in understanding how vaccines can be tailored for better effectiveness and safety.

What is the effectiveness track record for the Yellow Fever Virus Vaccine?

Research shows that the Yellow Fever Vaccine effectively triggers a strong immune response. Studies have found that it can create a robust T cell response, similar to the body's reaction during a real viral infection. This suggests the vaccine prepares the body to fight the virus if encountered. One study predicted, using a detailed scientific approach, that the vaccine would lead to strong immune responses in people, reinforcing confidence in its effectiveness against yellow fever. Additionally, the Yellow Fever Vaccine has been used since 1937, supporting its safety and effectiveness over many years. Participants in this trial will receive the Yellow Fever Vaccine, with some arms including additional procedures such as leukapheresis or fine needle aspirate to further study the immune response. ^{1 2 6 7 8}

Who Is on the Research Team?

Rafi Ahmed, PhD

Principal Investigator

Emory University

Sri Edupuganti, MD, MPH

Principal Investigator

Emory University

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

Group I: Arm D: Yellow Fever Vaccine in HLA-A202- Participants Experimental Treatment 1 Intervention

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

Group II: Arm C: Yellow Fever Vaccine and Fine Needle Aspirate in HLA-A202+ Participants Experimental Treatment 2 Interventions

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

Group III: Arm B: Yellow Fever Vaccine and Leukapheresis in HLA-A202+ Participants Experimental Treatment 2 Interventions

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

Group IV: Arm A: Yellow Fever Vaccine in HLA-A202+ Participants Experimental Treatment 1 Intervention

HLA-A202+ participants receiving the 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+

Published Research Related to This Trial

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]

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]

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 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]

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]

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]

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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8475614/

Yellow fever virus vaccination: an emblematic model to ... It also induces a strong T cell response resembling the ones of acute infections, in contrast to most other vaccines. In spite of its use since 1937, learning ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4049462/

Systems biology approach predicts immunogenicity of the ... Here we have used a systems biology approach to identify early gene 'signatures' that predicted immune responses in humans vaccinated with yellow fever vaccine ...

3. fda.gov fda.gov/media/76015/download

YF-VAX® - Yellow Fever Vaccine For further discussion of vaccination with YF-VAX during pregnancy and for documentation of a protective immune response to vaccine where it is deemed essential ...

4. nature.com nature.com/articles/s41541-024-00836-w

Immune response induced by standard and fractional ... Accordingly, previous studies suggest the ability of subdoses of yellow fever vaccine to induce a CD8+ T-mediated cellular immunity as those ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S2352396424003682

Articles Next generation yellow fever vaccine induces an ... This first-in-human study shows that vYF, across all doses assessed, induces strong innate antiviral responses and adaptive B cell responses similar to those ...

6. cdc.gov cdc.gov/yellow-fever/hcp/vaccine/index.html

Yellow Fever Vaccine Information for Healthcare Providers If simultaneous administration is not possible, wait 30 days between vaccinations, because the immune response to a live viral vaccine could be ...

7. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1473309923008095

Immunological response to fractional-dose yellow fever ... A fractional dose of the 17DD yellow fever vaccine induced an immunologic response with detectable titres at 5 years among the majority of participants in the ...

8. nature.com nature.com/articles/s41541-022-00595-6

A phase I clinical study to assess safety and ... The immune responses showed that the SII YFV was highly immunogenic by both SC and IM routes and the GMTs in both groups were comparable to ...