Virulence phenotype and genetic characteristics of the T 32-ISTRATI Shigella flexneri 2a vaccine strain

Abstract

The T 32-ISTRATI strain, which has been used as an oral attenuated Shigella flexneri 2a vaccine, has lost the invasive phenotype due to a spontaneous deletion in the shigella virulence plasmid. This deletion has eliminated three plasmid loci ( ipaBCDA, invA and virG) that are necessary for production of a positive Sereny test by Shigella species. Virulence in the Sereny test was reconstituted in the T 32-ISTRATI strain by the conjugal transfer of an intact 140 MDa virulence plasmid from S. flexneri 5. The T 32-ISTRATI vaccine is safe when given orally in multiple doses of 50–100 × 10 9 organisms, and both homologous and heterologous protection has been reported in large Romanian and Chinese field trials. Although the protective antigen(s) in this vaccine have not been identified, the potential use of non-invasive plasmid deletion mutants as living shigella vaccines is illustrated by the T 32-ISTRATI vaccine.