Developing a new vaccine strategy with prophylactic properties against hemolytic uremic syndrome (HUS) associated with strains of enterohaemorrhagic Escherichia coli (EHEC) produced by \Shiga-like \(Stx).

Author(s)

Robert Leonardo Gálvez Rojas

• Document type: Doctoral Thesis
• Press: São Paulo.
• Institution: Universidade de São Paulo (USP). Instituto de Ciências Biomédicas (ICB/SDI)
• Defense date: 2010-12-14

Examining board members

Rita de Cassia Cafe Ferreira; Antonio Fernando Pestana de Castro; Nilton Erbet Lincopan Huenuman; Marina Baquerizo Martinez; Marcia Ribeiro Pinto da Silva

• Advisor: Rita de Cassia Cafe Ferreira; Luis Carlos de Souza Ferreira

Abstract

The goal of this study was to develop a vaccine strategy of using Salmonella strains capable of expressing a nontoxic form of the main toxin associated with EHEC strains that cause hemolytic uremic syndrome. These strains of Salmonella differ in flagellin expression, the main structural unit of the flagellum. The strains were capable of expressing a nontoxic form of the protein \"Shiga-like\" within the bacteria and the extracellular space, showed high plasmid stability in vitro and in vivo and were able to increase the degree of intestinal colonization. Furthermore, we evaluated the immunogenic potential of these strains and found that immunization with three doses of salmonella were able to generate (IgA) humoral and (IgG) systemic antibodies with neutralizing properties in vitro and partial protection in vivo conditions facing trials challenges with the native toxin. We were unable to find significant differences in the immunogenic properties between these strains that differ in flagellin expression. Our results indicate that nontoxic forms of Stx2 expressed in biological vectors can be an alternative vaccine strategy to control the SHU. (AU)