Genetic stability of vaccine strain Salmonella Typhi Ty21a over 25 years

• Published in: International journal of medical microbiology Vol. 299; no. 4; pp. 233 - 246
• Main Authors: Kopecko, Dennis J, Sieber, Heike, Ures, Jose A, Fürer, Andreas, Schlup, Jacqueline, Knof, Ulrich, Collioud, Andre, Xu, DeQi, Colburn, Kevin, Dietrich, Guido
• Format: Journal Article
• Language: English
• Published: Germany Elsevier GmbH 01.04.2009
• Subjects: Biochemical characteristics; DNA, Bacterial - genetics; Genetic and phenotypic analyses; Genomic Instability; Humans; Infectious Disease; Medical Education; Mutation, Missense; Point Mutation; Salmonella enterica; Salmonella typhi - genetics; Salmonella Vaccines - genetics; Sequence Analysis, DNA; Typhoid fever vaccine; Vaccine strain Ty21a; Vaccines, Attenuated - genetics; Virulence Factors - genetics; Genetic and phenotypic analyses; Vaccine strain Ty21a; Typhoid fever vaccine
• ISSN: 1438-4221; 1618-0607
• DOI: 10.1016/j.ijmm.2008.09.003

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.