YF-VAX (yellow fever vaccine) / Sanofi - LARVOL DELTA

Formulation and stability design spaces for a new yellow fever vaccine. (PubMed, Eur J Pharm Biopharm) - "This study demonstrates that the combination of systematic excipient screening and advanced analytics enables the selection of robust formulations with long-term stability within an accelerated development timeframe. The developed vaccine formulation has the potential for large-scale industrial production and can address substantial market demand in the coming years, representing a significant advancement in vYF technology."

Journal

Immunogenicity and Safety of vYF, a Yellow Fever Vaccine - A Phase 2 Trial. (PubMed, N Engl J Med) - P2 | "In this trial, vYF had immunogenicity and safety profiles similar to those of YF-VAX. (Funded by Sanofi; ClinicalTrials.gov number, NCT04942210.)."

Clinical • Journal • P2 data • Infectious Disease

Effectiveness of the Local Additional Risk Minimisation Measures for Yellow Fever Vaccine in the United Kingdom: A Survey of Healthcare Professionals and Vaccinees. (PubMed, Pharmacoepidemiol Drug Saf) - "Three of the five effectiveness indicators were successful. Importantly, no YF vaccination errors were reported in the UK National Travel Health Network and Centre Annual Return reports (2021-2024) following aRMM implementation. Therefore, these findings suggest that the local aRMMs provide an effective framework for the safe administration of YF vaccine."

Journal

Phase 3 Single Arm, Open Study on vYF in Adults (clinicaltrials.gov) - P3 | N=254 | Completed | Sponsor: Sanofi Pasteur, a Sanofi Company | Active, not recruiting ➔ Completed

Trial completion

Phase 3 Randomized, Modified Double-blind, Active-controlled Safety Study on vYF in Adults (clinicaltrials.gov) - P3 | N=640 | Completed | Sponsor: Sanofi | Active, not recruiting ➔ Completed

Trial completion

Phase 3 Single Arm, Open Study on vYF in Adults (clinicaltrials.gov) - P3 | N=254 | Active, not recruiting | Sponsor: Sanofi Pasteur, a Sanofi Company | Recruiting ➔ Active, not recruiting | Trial completion date: Apr 2026 ➔ Dec 2025 | Trial primary completion date: Apr 2026 ➔ Dec 2025

Enrollment closed • Trial completion date • Trial primary completion date

Phase 3 Single Arm, Open Study on vYF in Adults (clinicaltrials.gov) - P3 | N=254 | Recruiting | Sponsor: Sanofi Pasteur, a Sanofi Company | Not yet recruiting ➔ Recruiting

Enrollment open

Phase 3 Single Arm, Open Study on vYF in Adults (clinicaltrials.gov) - P3 | N=254 | Not yet recruiting | Sponsor: Sanofi Pasteur, a Sanofi Company

New P3 trial

A Phase III Control Study of the Safety and Immunogenicity of vYF in Pediatric Population (clinicaltrials.gov) - P3 | N=2440 | Recruiting | Sponsor: Sanofi | Trial completion date: Oct 2029 ➔ Mar 2030

Trial completion date • Pediatrics

Phase 3 Randomized, Modified Double-blind, Active-controlled Safety Study on vYF in Adults (clinicaltrials.gov) - P3 | N=640 | Active, not recruiting | Sponsor: Sanofi | Recruiting ➔ Active, not recruiting | Trial completion date: Apr 2026 ➔ Jan 2026 | Trial primary completion date: Apr 2026 ➔ Jan 2026

Enrollment closed • Trial completion date • Trial primary completion date

A Phase III Control Study of the Safety and Immunogenicity of vYF in Pediatric Population (clinicaltrials.gov) - P3 | N=2440 | Recruiting | Sponsor: Sanofi

New P3 trial • Pediatrics

VYF02: Study on an Investigational Yellow Fever Vaccine Compared With YF-VAX in Adults in the USA (clinicaltrials.gov) - P2 | N=568 | Active, not recruiting | Sponsor: Sanofi Pasteur, a Sanofi Company | Trial completion date: Jun 2028 ➔ Jun 2027

Trial completion date

Phase 3 Randomized, Modified Double-blind, Active-controlled Safety Study on vYF in Adults (clinicaltrials.gov) - P3 | N=640 | Recruiting | Sponsor: Sanofi

New P3 trial

Next generation yellow fever vaccine induces an equivalent immune and transcriptomic profile to the current vaccine: observations from a phase I randomised clinical trial. (PubMed, EBioMedicine) - P1 | "vYF-induced strong innate and adaptive immune responses comparable to those induced by YF-VAX, with similar transcriptomic and kinetic profiles observed."

Journal • P1 data • CD4 • CXCL10

Safety and immunogenicity of a next-generation live-attenuated yellow fever vaccine produced in a Vero cell line in the USA: a phase 1 randomised, observer-blind, active-controlled, dose-ranging clinical trial. (PubMed, Lancet Infect Dis) - "vYF has a similar safety and immunogenicity profile to YF-VAX. In general, the vYF 5 Log CCID50 dose appeared to show optimal viraemia, safety, and immunogenicity, and was chosen for subsequent development."

Journal • P1 data • Preclinical • Dermatology • Infectious Disease • Pain

Study on an Investigational Yellow Fever Vaccine Compared With Stamaril in Adults in Europe and Asia (clinicaltrials.gov) - P2 | N=690 | Active, not recruiting | Sponsor: Sanofi Pasteur, a Sanofi Company | Trial completion date: Apr 2028 ➔ Apr 2027

Trial completion date

6-month Safety and Immunogenicity follow-up of an Investigational Yellow fever Vaccine in Adults (ASTMH 2023) - "A high seroprotection rate was maintained for at least 6 months after a single dose of v YF in 18-60 years old individuals, as in YF-VAX vaccinees with no safety concerns. (BB-IND: IND #: 019167; WHO UTN: U1111-1261-5612)"

Clinical • Late-breaking abstract

"@sanofi @IndiaSanofi plz update on Yellow Fever vaccine availability in India." (,@damlesafaris)

Clinical

Enhanced safety surveillance of STAMARIL® yellow fever vaccine provided under the expanded access investigational new drug program in the United States. (PubMed, J Travel Med) - "This study supports the utility of STAMARIL in the EAP as an alternative solution for the yellow fever vaccine shortage in USA. SAEs were very rare and consistent with the known safety profile of STAMARIL."

IND • Journal

Evaluation of safety and immuno-efficacy of a next generation live-attenuated yellow fever vaccine in cynomolgus macaques. (PubMed, Vaccine) - "Additionally, vYF provided effective resistance to virulent challenge with wild-type YFV Asibi including complete protection against YFV-induced mortality, pathology, dysregulation of blood and liver soluble biomarkers, and a significant reduction in viremia and viral load to the limit of detection. These NHP data suggest that vYF would provide protection against YFV infection in practice, at least similar to that achieved with currently marketed YF-17D vaccines."

Journal • Infectious Disease

Study on an Investigational Yellow Fever Vaccine Compared With Stamaril in Adults in Europe and Asia (clinicaltrials.gov) - P2 | N=690 | Active, not recruiting | Sponsor: Sanofi Pasteur, a Sanofi Company | Trial completion date: Apr 2027 ➔ Apr 2028

Trial completion date

VYF02: Study on an Investigational Yellow Fever Vaccine Compared With YF-VAX in Adults in the USA (clinicaltrials.gov) - P2 | N=567 | Active, not recruiting | Sponsor: Sanofi Pasteur, a Sanofi Company | Trial completion date: Jan 2027 ➔ Jun 2028

Trial completion date

Absence of transmission of vYF next generation Yellow Fever vaccine in mosquitoes. (PubMed, PLoS Negl Trop Dis) - "Here we infected Aedes aegypti and Aedes albopictus mosquitoes with vYF-247 vaccine compared first to the YF-17D-204 reference Sanofi vaccines (Stamaril and YF-VAX) and a clinical human isolate S-79, provided in a blood meal at a titer of 6.5 Log ffu/mL and secondly, to the clinical isolate only at an increased titer of 7.5 Log ffu/mL. Although comparison of vYF-247 to reference vaccines could not be completed to yield significant results, we showed that vYF-247 was not transmitted by both Aedes species, either laboratory strains or field-collected populations, compared to clinical strain S-79 at the highest inoculation dose. Combined with the undetectable to low level viremia detected in vaccinees, transmission of the vYF-247 vaccine by mosquitoes is highly unlikely."

Journal • Infectious Disease

Low replication and absence of transmission of vYF next generation Yellow Fever Vaccine candidate in mosquitoes (ASTMH 2022) - "For the development of a new vaccine, WHO recommends to document infectivity and replication in mosquitoes in comparison with a current vaccine.Batches of 40 Aedes aegypti and Aedes albopictus mosquitoes were infected through a blood meal containing vYF vaccine in comparison with Stamaril, YF-VAX and wild type (wt) Dakar strain provided at 6.5 or 7.5 LogFFU/mL. These results were confirmed with field-collected mosquitoes from Asia, Latin America and Africa.Even if in some limited cases the vYF vaccine candidate could infect and to a very minor extent disseminate in mosquitoes, no transmission potential was detected. Together with the undetectable to low level viremia observed after vaccination of human volunteers, these data demonstrate that the dissemination of the vYF vaccine by mosquitoes is highly unlikely."

Late-breaking abstract • Hematological Disorders • Infectious Disease

Deep Characterization of the Immunogenicity Induced by Next Generation Yellow Fever Vaccine in Phase 1 Dose-Ranging Study (ASTMH 2022) - P1 | "Finally, a strong YF-specific memory B cell response with both IgM and IgG secreting cells was detected at D28 post-vaccination and IgG memory B cell response was maintained for at least 6 months. Overall, no difference was observed between the 3 doses: 4, 5 and 6 Log CCID50 and no difference was observed between vYF groups and YF-VAX vaccinees.Together these results show that vaccine take is similar for vYF and YF-VAX and it may suggest that the immune response to vYF could provide the same immune response over time and longevity as that induced by the reference vaccine."

P1 data