title: Genetic stability of vaccine strain Salmonella Typhi Ty21a over 25 years.
abstract: The attenuated live bacterial vaccine strain Salmonella enterica Serovar Typhi Ty21a is the main constituent of Vivotif, the only licensed oral vaccine against typhoid fever. The strain was developed in the 1970s by chemical mutagenesis. In the course of this mutagenesis, a number of mutations were introduced into the vaccine strain. Characterisation of the vaccine strain during development as well as release of master- and working seed lots (MSL and WSL) and commercial batches is based on phenotypic assays assessing microbiological and biochemical characteristics of Ty21a. In the current study, we have analysed by DNA sequencing the specific mutations originally correlated with the attenuation of strain Ty21a. These data demonstrate the stability of these mutations for MSLs and WSLs of Ty21a produced between 1980 and 2005. Finally, we have confirmed the correlation of these genetic mutations with the expected phenotypic attenuations for the seed lots used in vaccine manufacture over 25 years.
authors.affiliation: Laboratory of Enteric and Sexually Transmitted Diseases, Center for Biologics Evaluation and Research, Food and Drug Administration, 29 Lincoln Drive, NIH Campus, Bldg. 29/420, HFM440, Bethesda, MD 20892, USA.
authors.forename: Dennis J
authors.initials: DJ
authors.lastname: Kopecko
authors.forename: Heike
authors.initials: H
authors.lastname: Sieber
authors.forename: Jose A
authors.initials: JA
authors.lastname: Ures
authors.forename: Andreas
authors.initials: A
authors.lastname: Fürer
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Schlup
authors.forename: Ulrich
authors.initials: U
authors.lastname: Knof
authors.forename: Andre
authors.initials: A
authors.lastname: Collioud
authors.forename: Deqi
authors.initials: D
authors.lastname: Xu
authors.forename: Kevin
authors.initials: K
authors.lastname: Colburn
authors.forename: Guido
authors.initials: G
authors.lastname: Dietrich
mesh_terms: D004269:DNA, Bacterial / Q000235:genetics; D042822:Genomic Instability; D006801:Humans; D020125:Mutation, Missense; D017354:Point Mutation; D022562:Salmonella Vaccines / Q000235:genetics*; D012485:Salmonella typhi / Q000235:genetics*; D017422:Sequence Analysis, DNA; D014613:Vaccines, Attenuated / Q000235:genetics; D037521:Virulence Factors / Q000235:genetics
chemical_list: D004269:DNA, Bacterial; D022562:Salmonella Vaccines; D014613:Vaccines, Attenuated; D037521:Virulence Factors