Yellow fever vaccine: comparison of the neurovirulence of new 17D-204 Stamaril™ seed lots and RK 168-73 strain

Abstract

The neurovirulence of two new candidate 17D-204 Stamaril™ working seed lots and that of two reference preparations were compared. The Stamaril™ working seed lots have been used for more than twenty years for the manufacturing of vaccines of acceptable safety and efficacy. The preparation designated RK 168-73 and provided by the Robert Koch Institute was used as a reference. It was confirmed that RK 168-73 strain was not a good virus control in our study because it has a very low neurovirulence regarding both the clinical and histopathological scores in comparison with Stamaril™ strain and is not representative of a vaccine known to be satisfactory in use. The results were reinforced by the phenotypic characterization by plaque assay demonstrating that RK 168-73 was very different from the Stamaril™ vaccine, and by sequencing results showing 4 mutations between Stamaril™ and RK 168-73 viruses leading to amino acid differences in the NS4B and envelop proteins.

Keywords: 17D-204 Stamaril™; CIT; Centre International de Toxicologie; Eur. Ph; European Pharmacopoeia; FNV; French neurotropic vaccine; IABS; International Association for Biologicals symposium; Neurovirulence; RK 168-73; Seeds; TRS; Technical report series; Vaccine characterization; WHO; WSL; World Health Organization; YEL-AND; YEL-AVD; YF; Yellow Fever Vaccine-Associated Neurotropic Disease; Yellow Fever Vaccine-Associated Viscerotropic Disease; Yellow fever vaccine; working seed lot; yellow fever.