Development of new vaccine approaches against Hemolytic Uremic Syndrome (HUS) based nontoxic variants of Stx2 toxin of Enterohaemorrhagic Escherichia coli (EHEC).

Author(s)

Priscila Aparecida Dal Pozo Gomes

• Document type: Doctoral Thesis
• Press: São Paulo.
• Institution: Universidade de São Paulo (USP). Instituto de Ciências Biomédicas (ICB/SDI)
• Defense date: 2013-06-24

Examining board members

Rita de Cassia Cafe Ferreira; Beatriz Ernestina Cabilio Guth; Denise Silvina Piccini Quintas Horton; Roxane Maria Fontes Piazza; Enrique Mario Boccardo Pierulivo

• Advisor: Rita de Cassia Cafe Ferreira

Abstract

Shiga toxin (Stx)-producing Escherichia coli strains (STEC) cause the Hemolytic Uremic Syndrome (HUS), a severe illness. The Stx is an AB5 toxin and comprises a single catalytic A subunit, endowed with protein synthesis inhibitory effect, and five B subunits, involved in the binding to glycolipid receptors on the surface of target cells. The protein Stx2DAB was administered to mice combined with different adjuvants: a heat-labile toxin (LT), derived from enterotoxigenic E. coli (ETEC) strains, the flagellin FliCi of S. Typhimurium, alum or Freund\'s adjuvant. Additionally mice were immunized with denatured toxin. The results showed that sera from mice immunized with recombinant Stx2DAB plus Freund adjuvant displayed the highest anti-Stx2 antibody titers with maximum protection of 77% to a lethal challenge with the Stx2 holotoxin, however animals immunized with denatured toxin showed no protection, despite high serum titers achieved. The results show the potential protector of vaccine antigen as a vaccine subunit and the importance of conformation in the protection. (AU)