Phenotypic and genetic characterization of a next generation live-attenuated yellow fever vaccine candidate

• Published in: Vaccine Vol. 40; no. 38; pp. 5641 - 5650
• Main Authors: Esson, Raphael, Rodrigues De Sousa, Emanuel, Benair, Loic, Devard, Nicolas, Soulet, Damien, Gillet, Audrey, Bassard, Isabelle, Falque, Stephanie, Chareyre, Audrey, Marmin, Morgane, Girerd-Chambaz, Yves, Logvinoff, Carine, Navarro Sanchez, Martha Erika
• Format: Journal Article
• Language: English
• Published: Kidlington Elsevier Ltd 09-09-2022; Elsevier Limited
• Subjects: Amino acid sequence; Amino acids; Dengue fever; Fever; Genomes; Genomics; Immunization; Manufacturing; Manufacturing industry; Neurovirulence; Nucleotides; Phenotype; Phenotypes; Plaques; Sequence; Serum-free; Vaccines; Vector-borne diseases; Vero cells; Viral sequence; Virulence; Yellow fever; Yellow Fever vaccine; YF-VAX; France; Yellow Fever vaccine; Phenotype; YF-VAX; Serum-free; Sequence; Viral sequence; Neurovirulence; Vero cells
• ISSN: 0264-410X; 1873-2518
• DOI: 10.1016/j.vaccine.2022.07.043

•The vYF-247 vaccine candidate strain was obtained from YF-VAX by clone purification.•Genetic stability and consistency of vYF-247 was demonstrated during manufacture.•vYF-247 had a consistent small plaque size profile (<1 mm) during manufacture.•vYF-247 had a more attenuated neurovirulence phenotype during production than YF-VAX.•The safety profile of vYF-247 is anticipated to be favorable in clinical practice.
We assessed the genetic and phenotypic characteristics of a yellow fever vaccine candidate, which was cloned from a YF-VAX substrain selected for growth in Vero cells (vYF-247), during the manufacturing process from the master seed lot (MSL) and working seed lot (WSL) through to the drug substance (DS) stage. There were nine minor nucleotide variants observed from the MSL to the DS stage, of which five led to amino acid changes. The variant positions were, however, not known risks for any virulence modification. vYF-247 exhibits a homogenous plaque size profile (as expected for a cloned vaccine candidate) composed of small plaques (<1 mm) that remained consistent throughout the manufacturing process. In addition, there was no change in the viral replication rate. Of note, the DS sequences across the two manufacturing campaigns (2018 and 2019) were very similar suggesting a high batch-to-batch consistency. All MSL, WSL and DS batches exhibited similar neurovirulence profiles in mice and had a more attenuated neurovirulence phenotype than the YF-VAX (egg-based vaccine) comparator. Overall, the neurovirulence phenotype of vYF-247 does not change from MSL, WSL to DS. These data collectively support the safety and genetic stability of vYF-247 during the production process.