Development of a vaccine strategy against Shiga toxin (Stx) of Escherichia coli (EHEC) based on recombinant protein Stx2ΔAB incorporated into liposomes.

Author(s)

Monica Josiane Rodrigues de Jesus

• Document type: Master's Dissertation
• Press: São Paulo.
• Institution: Universidade de São Paulo (USP). Instituto de Ciências Biomédicas (ICB/SDI)
• Defense date: 2017-02-07

Examining board members

Luis Carlos de Souza Ferreira; Adriano Rodrigues Azzoni; Wagner Quintilio; Letícia Barboza Rocha

• Advisor: Luis Carlos de Souza Ferreira

Abstract

Infections associated with strains of enterohaemorrhagic Escherichia coli (EHEC), can cause clinical manifestations are the hemolytic uremic syndrome (HUS), the most severe complication. HUS is related to the presence of Shiga toxin type 2 (Stx2) and yet do not have a vaccine or effective treatments for use in humans. This work aimed to develop a vaccine based on non-toxic derivative containing the B subunit and the A2 portion of the subunit called Stx2ΔAB. After expression in E. coli strains and initial purification attempts resulted in the formation of protein aggregates. Adjustments in the cultivation and purification conditions have enabled the protein as the monomer subunit B but without the presence of the A2 portion. The antigen was incorporated into multilamellar liposomes (MLVs), the combined lipid A and administered subcutaneously to mice. immunized animals develop systemic antibodies specific against Stx2 able to neutralize toxin in vitro and to confer partial protection when challenged with a lethal dose of toxin. In conclusion, the study confirmed the potential vaccine antigen and validated strategy based on antigen incorporation into MLVs as immunization strategy. (AU)

• FAPESP's process: 14/21141-4 - Development of a vaccine strategy against Shiga toxin of enterohemorrhagic Escherichia coli (EHEC) based recombinant protein Stx2AB incorporated into liposomes
• Grantee: Mônica Josiane Rodrigues de Jesus
• Support Opportunities: Scholarships in Brazil - Master