Journal article
Immunogenicity and Safety of vYF, a Yellow Fever Vaccine - A Phase 2 Trial
The New England journal of medicine, Vol.394(14), pp.1399-1408
04/09/2026
DOI: 10.1056/NEJMoa2505665
PMID: 41950474
Abstract
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.
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.
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.
In this trial, vYF had immunogenicity and safety profiles similar to those of YF-VAX. (Funded by Sanofi; ClinicalTrials.gov number, NCT04942210.).
Details
- Title: Subtitle
- Immunogenicity and Safety of vYF, a Yellow Fever Vaccine - A Phase 2 Trial
- Creators
- Emmanuel Feroldi - Sanofi (France)Mark J Mulligan - NYU Langone HealthKawsar R Talaat - Johns Hopkins UniversityChen Sabrina Tan - University of IowaKristopher Paolino - SUNY Upstate Medical UniversitySrilatha Edupuganti - Emory UniversityMatthew H Collins - Emory UniversitySarah L George - Saint Louis UniversityMatthew Davis - Rochester Clinical Research, Rochester, NYBrandon Essink - Meridian Clinical ResearchRobert Jeanfreau - MedPharmics, Metairie, LAJames Peterson - Foothill Family ClinicDavid Fried - Velocity Clinical Research (United States)Ada-Maria Minutello - Sanofi (France)Sandrine Orlando - Sanofi (France)Joanna Korejwo - Sanofi (France)Andrey Rojas - Asociación Colombiana de Facultades de IngenieríaMarine Dufournet - Sanofi (France)Tifany Machabert - Sanofi (France)Louis Devlin - Sanofi (United States)Carina Frago - Sanofi, SingaporevYF Vaccine Study Team
- Resource Type
- Journal article
- Publication Details
- The New England journal of medicine, Vol.394(14), pp.1399-1408
- DOI
- 10.1056/NEJMoa2505665
- PMID
- 41950474
- NLM abbreviation
- N Engl J Med
- ISSN
- 0028-4793
- eISSN
- 1533-4406
- Publisher
- Massachusetts Medical Society
- Grant note
- Sanofihttp://dx.doi.org/10.13039/100004339
We thank the staff of each investigational site and particularly the participants who volunteered for this phase 2 clinical trial; the VYF02 clinical team members within Sanofi, along with Manuel Vangelisti, Lucia Perez, Marcela Cangrejo Sanchez, Nuchra Sirisuphmitr, Sonia Benamor, Caroline Rossoni, and Pascale Davaux, who contributed to the trial outcome; the following trial staff: Heekoung Youn, Mahnoor Ali, Ashanay Allen, Mala Begum, Lisa Zhao, Pamela Suman, Jacqueline Callahan, Stephanie Rettig, Abdonnie Holder, James Wilson, Trishala Karmacharya, Meron Tasissa, Shelby Goins, Samantha Yip, Julia Wagner, Michael Tuen, Samuel Nweke, Sarah Haiken, Emilie Geesey, Miguel Rodriguez, Abdul Abdulai, Miilani Yonatan, Kathryn Jano, and Grace Yip; and Holly McAlister and Nichola Cruickshanks of Springer Health+ and Isabel Gregoire on behalf of Sanofi for editorial assistance with an earlier version of the manuscript.
- Language
- English
- Date published
- 04/09/2026
- Academic Unit
- Microbiology and Immunology; Infectious Diseases; Iowa Neuroscience Institute; Internal Medicine
- Record Identifier
- 9985153531102771
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