Yellow Fever Vaccine for Yellow Fever

No longer recruiting at 1 trial location

Overseen By Kevin Escandon, MD, MSc

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: University of Minnesota

Must not be taking: Immunosuppressants, Corticosteroids, TNF inhibitors, others

Disqualifiers: Yellow fever history, Bleeding disorder, Immunosuppression, others

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

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how the yellow fever vaccine affects the immune system, with a focus on the impact of infections on immune responses. Researchers will study individuals from Uganda and Minnesota, collecting samples before and after vaccination to understand the relationship between infections and vaccine response. Participants must not have had yellow fever or received its vaccine and must not be immunosuppressed. As a Phase 1 and Phase 2 trial, this research aims to understand the vaccine's function and measure its effectiveness in a smaller group, offering participants a chance to contribute to groundbreaking vaccine research.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but if you are on immunosuppressive drugs, you may not be eligible to participate.

Is there any evidence suggesting that the Yellow Fever Vaccine is likely to be safe for humans?

Research has shown that the yellow fever vaccine is generally safe, but some risks exist. Most people experience mild side effects such as headaches, muscle aches, or a slight fever. However, in rare instances, the vaccine can cause serious health problems, including severe allergic reactions that might affect organs like the liver or kidneys.

Although uncommon, these serious reactions have occurred. Out of 23 reported serious cases, 14 were fatal. It is important to weigh these risks against the benefits, especially in areas where yellow fever poses a threat. Discuss any concerns or health conditions with a healthcare provider to understand how they might affect your reaction to the vaccine. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the Yellow Fever Vaccine because it offers a promising solution to protect against yellow fever, a potentially deadly viral infection. Unlike other treatments that primarily focus on managing symptoms once infected, this vaccine aims to prevent the disease altogether by stimulating the immune system to build a defense before exposure. Vaccination remains the most effective strategy for controlling yellow fever outbreaks, and this new vaccine is being studied to ensure it provides robust and long-lasting immunity with potentially fewer side effects.

What evidence suggests that the Yellow Fever Vaccine might be an effective treatment for Yellow Fever?

Research has shown that the yellow fever vaccine is highly effective. A single shot can provide lifelong protection, with 80–100% of individuals becoming immune within 10 days. Over 99% of those vaccinated gain protection shortly after receiving the shot. This indicates that the vaccine effectively guards against yellow fever for nearly everyone who receives it. Instances where the vaccine fails are rare, underscoring its strong success rate. ^{6 7 8 9 10}

Who Is on the Research Team?

Timothy Schacker, MD

Principal Investigator

University of Minnesota

Are You a Good Fit for This Trial?

This trial is for healthy adults without immune system issues who haven't had the yellow fever vaccine before. Women of childbearing age must avoid pregnancy for a month after vaccination. People with bleeding disorders, severe allergies to vaccine components, or those on immunosuppressive therapy cannot join.

Inclusion Criteria

I am not on any medication that weakens my immune system.

If female of childbearing age must agree to contraception for one month following administration of the vaccination.

Exclusion Criteria

I am immunosuppressed due to a condition like HIV, cancer, or from receiving a transplant or certain medications.

You have a mental or behavioral disorder that could make it hard for you to finish the study, as determined by the investigator.

I plan to try for a baby within 28 days of joining the study and getting the yellow fever vaccine.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Pre-Vaccination Assessment

Participants undergo lymph node and adipose tissue biopsy and leukapheresis before vaccination

1 week

Vaccination

Participants receive the yellow fever vaccine

1 day

Post-Vaccination Assessment

Participants undergo a second lymph node biopsy and leukapheresis 3 weeks after vaccination

3 weeks

Follow-up

Participants are monitored for safety and effectiveness, with regular collection of PBMC, plasma, urine, and stool over 18 months

18 months

What Are the Treatments Tested in This Trial?

Interventions

• Yellow Fever Vaccine

Trial Overview The study tests how the yellow fever vaccine affects lymph node structures and immunity in two groups: one from Uganda and another from Minnesota. It involves blood samples and tissue collection before and after vaccination to assess inflammation and immune response.

How Is the Trial Designed?

Group I: All Participants Experimental Treatment 1 Intervention

In this single-arm study, all participants will receive the intervention

Who Is Running the Clinical Trial?

University of Minnesota

Lead Sponsor

Trials

1,459

Recruited

1,623,000+

National Institute of Allergy and Infectious Diseases (NIAID)

Collaborator

Trials

3,361

Recruited

5,516,000+

Published Research Related to This Trial

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 17D-204 and 17DD substrains of the yellow fever vaccine induce strong cellular and humoral immune responses, demonstrating similar immunogenicity, which is crucial for effective protection against yellow fever.

The adverse effects of both vaccines are mostly mild, indicating that they are safe options for vaccination, especially important given the recent re-emergence of yellow fever in certain regions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The 17D-204 and 17DD yellow fever vaccines: an overview of major similarities and subtle differences. Ferreira, CC., Campi-Azevedo, AC., Peruhype-Magalhāes, V., et al.[2019]

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]

Citations

1. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0264410X24011058

A comprehensive review of yellow fever vaccine ... Among cases confirmed by either RT-PCR or IgM-ELISA, 3.3 % (2/60) were breakthrough infections, with symptom onset >20 days- and 16 years- post ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9147422/

A Systematic Review and a Meta-Analysis of the Yellow ... The results obtained through the meta-analysis showed a risk of serious adverse events after yellow fever vaccination three times higher for the elderly.

3. thelancet.com thelancet.com/journals/langlo/article/PIIS2214-109X(23)00556-9/fulltext

Long-term immunity following yellow fever vaccination The pooled seroprotection rate was 47% (35–60) in children (aged 9–23 months at time of vaccination) and 61% (38–82) in people living with HIV.

4. who.int who.int/news-room/fact-sheets/detail/yellow-fever

Yellow fever A single dose provides lifelong immunity and no booster is needed. Immunity develops in for 80–100% of people within 10 days, and in over 99% ...

5. cdc.gov cdc.gov/acip/grade/yf-vac-boost.html

Grading of Recommendations, Assessment, Development ... A primary dose of YF vaccine is effective with very few vaccine failures documented and most (92%) of vaccine recipients maintaining ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4635904/

Serious adverse events associated with yellow fever vaccine Yellow fever vaccine was considered one of the safest vaccines, but in recent years it was found that it could rarely cause invasive and disseminated disease.

7. who.int who.int/groups/global-advisory-committee-on-vaccine-safety/topics/yellow-fever-vaccines/safety

Safety Altogether, 14 (61%) of the 23 cases have been fatal. All cases were reported after the primary yellow fever vaccination. Recent risk estimates for yellow fever ...

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

Yellow Fever Vaccine Information for Healthcare Providers Reactions to yellow fever vaccine are generally mild and include headaches, myalgias, and low-grade pyrexia. There have been reports of rare but ...

9. fda.gov fda.gov/media/76015/download

YF-VAX® - Yellow Fever Vaccine (See CONTRAINDICATIONS and ADVERSE REACTIONS sections.) Adverse reactions to YF-VAX include mild headaches, myalgia, low-grade fevers, or other minor symptoms ...

10. mayoclinic.org mayoclinic.org/drugs-supplements/yellow-fever-vaccine-subcutaneous-route/description/drg-20066731

Yellow fever vaccine (subcutaneous route) - Side effects & ... This vaccine may cause serious allergic reactions affecting multiple body organs (e.g., liver or kidney). Check with your doctor right away if ...