Salmonella Typhimurium vaccine strains encoding a non-toxic Stx2 induce partial protective immunity to the toxin expressed by enterohemorragic Escherichia coli (EHEC).

ROJAS RLG; GOMEZ PADP; BENTANCOR L; SBROGIO-ALMEIDA ME; COSTA SO; MASSIS LM; FERREIRA RCC; PALERMO MS; FERREIRA LCS

Clinical and vaccine Immunology

American Association for Microbiology

Lugar: Washington DC; Año: 2010 vol. 17 p. 529 - 536

Shiga-like toxin 2 (Stx2)-producing enterohaemorragic Escherichia coli (EHEC  or STEC) strains are the primary etiologic agents of the hemolytic uremic syndrome (HUS) which leads to renal failure and high mortality rates. Expression of Stx2 is the most relevant virulence-associated factor of EHEC strains and toxin neutralization, by antigen-specific serum antibodies, represents the main target for both preventive and therapeutic anti-HUS approaches. In the present report we describe two aroA Salmonella enterica  sv Typhimurium vaccine strains expressing a plasmid-encoded non-toxic derivative of Stx2 (Stx2ÄAB), containing the complete non-toxic A2 subunit and the receptor binding B subunit. The two S. Typhimurium strains differ in the expression of flagellin, the structural subunit of the flagellar shaft endowed with strong adjuvant effects. The vaccine strains expressed Stx2ÄAB, either cell-bound or secreted into the extracellular environment, and showed enhanced mouse gut colonization and high plasmid stability both under in vitro and in vivo conditions.  Mice orally immunized with three doses of the S. Typhimurium vaccine strains elicited serum (IgG) anti-Stx2B antibodies that neutralize the toxic effects of the native toxin tested under in vitro (Vero cells) conditions and confer partial protection under in vivo conditions. No significant difference regarding gut colonization and induction of antigen-specific antibody responses were detected in mice vaccinated with flagellated and non-flagellated bacterial strains. The present results indicate that expression of Stx2ÄAB by attenuated S. Typhimurium strains is an alternative vaccine approach for HUS control but additional improvements concerning the immunogenicity of Stx2 toxoids are still required.