Investigational Yellow Fever Vaccine vs Standard Vaccine for Yellow Fever

(VYF02 Trial)

Recruiting at 22 trial locations

Overseen By Trial Transparency email recommended (Toll free number for US & Canada)

Age: 18 - 65

Sex: Any

Trial Phase: Phase 2

Sponsor: Sanofi Pasteur, a Sanofi Company

Must not be taking: Immunosuppressants, Antivirals

Disqualifiers: Immunodeficiency, Flavivirus, Hepatitis B/C, 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

Compensation: Varies

Number of Visits: 2

567 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing a new yellow fever vaccine (vYF) against an existing one (YF-VAX) in people who have never been vaccinated for yellow fever. The goal is to see if the new vaccine can effectively trigger the immune system to produce antibodies, similar to the existing vaccine. YF-VAX is a well-established yellow fever vaccine that has been shown to be effective in producing protective antibodies.

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 therapy, long-term corticosteroids, or have taken any anti-viral medications recently, you may not be eligible to participate.

What data supports the effectiveness of the investigational yellow fever vaccine produced on serum-free Vero cells?

Research on a similar yellow fever vaccine, adapted for growth in Vero cells, showed it was safe and effective in animal studies, providing strong immune responses and protection against the virus. This suggests that the investigational vaccine could offer similar protection. ^{1 2 3 4 5}

Is the investigational yellow fever vaccine safe for humans?

The yellow fever vaccine, including the 17D and 17DD strains, is generally considered safe, but rare serious adverse events have been reported, such as hypersensitivity reactions and, in very rare cases, fatal haemorrhagic fever. ^{6 7 8 9 10}

How is the investigational yellow fever vaccine different from the standard vaccine?

The investigational yellow fever vaccine is unique because it is produced using Vero cells in serum-free media, unlike the standard vaccine which uses embryonated eggs. This method helps address vaccine shortages and has shown to provide effective protection similar to the current vaccines. ^{3 4 5 11 12}

Research Team

Clinical Sciences & Operations

Principal Investigator

Sanofi Pasteur, a Sanofi Company

Eligibility Criteria

Adults aged 18-60 in the USA who've never had yellow fever or a vaccine against it can join. Women must not be pregnant/breastfeeding, use contraception, and have negative pregnancy tests before/during the study. Participants should be free of certain infections, immune conditions, and not taking specific medications.

Inclusion Criteria

I am not able to have children because I am postmenopausal for over a year or have been surgically sterilized.

Informed consent form has been signed and dated.

You are of childbearing potential and agree to use an effective contraceptive method or abstinence from at least 4 weeks prior to vaccination until at least 4 weeks after vaccination

Exclusion Criteria

I or someone in my family has had issues with the thymus.

Known systemic hypersensitivity to any of the vaccine components, eggs, or history of a life-threatening reaction to the vaccines used in the study or to a vaccine containing any of the same substances.

I haven't had vaccines 4 weeks before or plan to within 4 weeks after the study vaccine, except for flu shots.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Vaccination

Participants receive one injection of either vYF or YF-VAX on Day 1

1 day

1 visit (in-person)

Immediate Observation

Participants are monitored for immediate adverse events for 30 minutes post-vaccination

30 minutes

1 visit (in-person)

Short-term Follow-up

Participants are monitored for solicited and unsolicited adverse events and seroconversion up to 6 months

6 months

Long-term Follow-up

Participants are monitored for related serious adverse events and seroconversion annually up to 5 years

5 years

Treatment Details

Interventions

• Yellow fever vaccine (produced on serum-free Vero cells)

Trial Overview The trial is testing a new yellow fever vaccine made with Vero cells against the standard YF-VAX. It measures if people's bodies respond similarly to both vaccines by looking at antibodies after 28 days and monitors safety over time.

Participant Groups

Group I: vYF Experimental Treatment 1 Intervention

1 injection of vYF at Day 1

Group II: YF-VAX Active Control 1 Intervention

1 injection of YF-VAX at Day 1

Who Is Running the Clinical Trial?

Sanofi Pasteur, a Sanofi Company

Lead Sponsor

Trials

429

Recruited

6,140,000+

Paul Hudson

Sanofi Pasteur, a Sanofi Company

Chief Executive Officer since 2019

Degree in Economics from Manchester Metropolitan University

Dr. Thomas Triomphe

Sanofi Pasteur, a Sanofi Company

Chief Medical Officer since 2020

MD from Tehran University of Medical Sciences

Findings from Research

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]

Two fatal cases of hemorrhagic fever were reported in Brazil following the yellow fever 17DD vaccine, highlighting a rare but serious complication associated with this vaccine.

The cases involved a 5-year-old girl and a 22-year-old woman, both of whom exhibited severe symptoms and died shortly after vaccination, suggesting that individual host factors may play a role in these adverse reactions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Serious adverse events associated with yellow fever 17DD vaccine in Brazil: a report of two cases. Vasconcelos, PF., Luna, EJ., Galler, R., et al.[2019]

References

1. Japan pubmed.ncbi.nlm.nih.gov

[Development of new Japanese encephalitis vaccine]. [2011]

2. Netherlands pubmed.ncbi.nlm.nih.gov

Cross-protection elicited by primary and booster vaccinations against Japanese encephalitis: a two-year follow-up study. [2013]

3. Switzerland pubmed.ncbi.nlm.nih.gov

T Cell-Mediated Immunity towards Yellow Fever Virus and Useful Animal Models. [2018]

4. Netherlands pubmed.ncbi.nlm.nih.gov

Evaluation of safety and immuno-efficacy of a next generation live-attenuated yellow fever vaccine in cynomolgus macaques. [2023]

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

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

6. Netherlands pubmed.ncbi.nlm.nih.gov

Active and passive surveillance of yellow fever vaccine 17D or 17DD-associated serious adverse events: systematic review. [2018]

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

Yellow Fever Immunizations: Indications and Risks. [2020]

8. Switzerland pubmed.ncbi.nlm.nih.gov

An Atypical Local Vesicular Reaction to the Yellow Fever Vaccine. [2020]

9. Brazil pubmed.ncbi.nlm.nih.gov

Factors associated with severity of adverse events following yellow fever vaccination during the biggest outbreak of the disease recorded in Brazil, 2016-2017. [2021]

10. England pubmed.ncbi.nlm.nih.gov

Serious adverse events associated with yellow fever 17DD vaccine in Brazil: a report of two cases. [2019]

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

Long-Term Protection After Fractional-Dose Yellow Fever Vaccination: Follow-up Study of a Randomized, Controlled, Noninferiority Trial. [2019]

12. Brazil pubmed.ncbi.nlm.nih.gov

Reactogenicity of yellow fever vaccines in a randomized, placebo-controlled trial. [2019]