Abstract
Attenuated Salmonella enterica serovar Typhi strain Ty21a is an important vaccine for controlling typhoid fever and serves as an oral vector for delivering heterologous antigens. The key attenuating features of this randomly mutated strain remain in question. Genome sequencing has revealed 679 single nucleotide polymorphisms (SNPs), and will help define alterations contributing to Ty21a safety and immunogenicity.
Highlights
Attenuated Salmonella enterica serovar Typhi strain Ty21a is an important vaccine for controlling typhoid fever and serves as an oral vector for delivering heterologous antigens
A 98% complete Ty21a genomic sequence was derived using a NimbleGen chip-based resequencing analysis compared to the published Ty2 genome (NCBI accession number AE014613); this approach resulted in numerous uncalled nucleotides
A Ty21a genomic sequence obtained from 4ϫ coverage by random 454-based sequencing was determined
Summary
Attenuated Salmonella enterica serovar Typhi strain Ty21a is an important vaccine for controlling typhoid fever and serves as an oral vector for delivering heterologous antigens. Prior genomic sequencing of Salmonella enterica serovar Typhi [1,2,3] has both stimulated research and increased our understanding of typhoid pathogenesis. Development of the live, attenuated Salmonella enterica serovar Typhi strain Ty21a [6] validated the concept that orally delivered, attenuated enteric bacteria can mimic natural infection in stimulating both mucosal and systemic immune responses without causing disease symptoms [7].
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