Immunogenicity and Safety of vYF, a Yellow Fever Vaccine - A Phase 2 Trial

Clinical Snapshot

Key Findings

• P Value: Not reported, but noninferiority criterion met

• Effect Size: Difference of 0.3 percentage points favoring vYF

• Primary Outcome: Seroconversion at day 29: vYF 99.7% vs YF-VAX 99.4%

• Nnt Or Sensitivity: Noninferiority demonstrated with lower CI limit (-1.2%) above the -5% margin

• Confidence Interval: 95% CI: -1.2 to 3.2 percentage points

Clinical Application

High feasibility if approved - single injection with similar administration requirements to current vaccine Relevant for Australian travelers to yellow fever endemic areas. Would require TGA approval. Could improve vaccine supply reliability for travel medicine clinics and reduce dependence on current vaccine supply chains. Adults 18-60 years requiring yellow fever vaccination for travel or occupational exposure

Abstract

BACKGROUND: A next-generation, live-attenuated yellow fever vaccine, vYF, was developed in Vero cells to improve vaccine supply and availability. The safety of and immune response to vYF as compared with those of the licensed yellow fever vaccine, YF-VAX, are unclear. METHODS: In this year 1 interim analysis of a phase 2, observer-blinded, randomized, active-controlled trial, we randomly assigned healthy adults 18 to 60 years of age in a 2:1 ratio to receive vYF or YF-VAX as a single vaccine injection on day 1. Neutralizing antibody titers were measured on day 29, month 6, and year 1. The primary analysis focused on the per-protocol population, which included participants with no history of yellow fever infection or vaccination and with no protocol deviations. Noninferiority would be shown if the lower limit of the two-sided 95% confidence interval of the between-group difference in the percentage of participants with seroconversion was greater than -5 percentage points on day 29. RESULTS: A total of 568 participants were enrolled: 382 in the vYF group and 186 in the YF-VAX group; 329 and 156 participants, respectively, were included in the per-protocol population for the noninferiority analysis. Seroconversion by day 29 occurred in 99.7% of participants receiving vYF and 99.4% of those receiving YF-VAX (difference, 0.3 percentage points; 95% confidence interval, -1.2 to 3.2, which met the criterion for noninferiority). Neutralizing antibody geometric mean titers were similar in the two vaccine groups, peaking on day 29 (in the vYF group, 1:2654 among participants with no history of yellow fever infection or vaccination and 1:1312 among participants with a history of yellow fever infection or vaccination; in the YF-VAX group, 1:3147 and 1:1079, respectively), then decreasing through 1 year after vaccination (in the vYF group, 1:401 among participants with no history of yellow fever infection or vaccination and 1:490 among participants with a history of yellow fever infection or vaccination; in the YF-VAX group, 1:548 and 1:646, respectively). No major safety concerns were identified. The safety profiles were similar in the two vaccine groups: solicited adverse events were reported by 208 of 367 participants (56.7%) in the vYF group and 113 of 185 participants (61.1%) in the YF-VAX group, and unsolicited adverse events were reported by 99 of 379 participants (26.1%) and 39 of 186 participants (21.0%), respectively. CONCLUSIONS: In this trial, vYF had immunogenicity and safety profiles similar to those of YF-VAX. (Funded by Sanofi; ClinicalTrials.gov number, NCT04942210.).

References

1. 1.Feroldi, E., Mulligan, M. J., Talaat, K. R., Tan, C. S., Paolino, K., Edupuganti, S., Collins, M. H., George, S. L., Davis, M., Essink, B., Jeanfreau, R., Peterson, J., Fried, D., Minutello, A. M., Orlando, S., Korejwo, J., Rojas, A., Dufournet, M., Machabert, T., Devlin, L., & Frago, C. (2026). Immunogenicity and Safety of vYF, a Yellow Fever Vaccine - A Phase 2 Trial. New England Journal of Medicine. https://doi.org/10.1056/NEJMoa2505665