Immunization with a Chimera Consisting of the B Subunit of Shiga Toxin Type 2 and Brucella Lumazine Synthase Confers Total Protection against Shiga Toxins in Mice.

Authors
Mejias, Maria Pilar; Ghersi, Giselle; Craig, Patricio Oliver; Panek, Cecilia Analia; Bentancor, Leticia Veronica; Baschkier, Ariela; Goldbaum, Fernando Alberto; Zylberman, Vanesa; Palermo, Marina Sandra
Publication Year
2013
Language
English
Format
article
Status
Published version
Description
The striking feature of enterohemorrhagic Escherichia coli (EHEC) infections is the production of Shiga toxins (Stx) implicated in the development of the life-threatening hemolytic uremic syndrome. Despite the magnitude of the social impact of EHEC infections, no licensed vaccine or effective therapy is available for human use. One of the biggest challenges is to develop an effective and safe immunogen to ensure nontoxicity, as well as a strong input to the immune system to induce long-lasting, high-affinity Abs with anti-Stx–neutralizing capacity. The enzyme lumazine synthase from Brucella spp. (BLS) is a highly stable dimer of pentamers and a scaffold with enormous plasticity on which to display foreign Ags. Taking into account the advantages of BLS and the potential capacity of the B subunit of Stx2 to induce Abs that prevent Stx2 toxicity by blocking its entrance into the host cells, we engineered a new immunogen by inserting the B subunit of Stx2 at the amino termini of BLS. The resulting chimera demonstrated a strong capacity to induce a long-lasting humoral immune response in mice. The chimera induced Abs with high neutralizing capacity for Stx2 and its variants. Moreover, immunized mice were completely protected against i.v. Stx2 challenge, and weaned mice receiving an oral challenge with EHEC were completely protected by the transference of immune sera. We conclude that this novel immunogen represents a promising candidate for vaccine or Ab development with preventive or therapeutic ends, for use in hemolytic uremic syndrome–endemic areas or during future outbreaks caused by pathogenic strains of Stx-producing E. coli.
Fil: Mejias, Maria Pilar. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental; Argentina
Fil: Ghersi, Giselle. Inmunova S.a; Argentina
Fil: Craig, Patricio Oliver. Fundación Instituto Leloir; Argentina
Fil: Panek, Cecilia Analia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental; Argentina
Fil: Bentancor, Leticia Veronica. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental; Argentina
Fil: Baschkier, Ariela. Dirección Nacional de Institutos de Investigación. Administración Nacional de Laboratorios e Institutos de Salud. Instituto Nacional de Enfermedades Infecciosas; Argentina
Fil: Goldbaum, Fernando Alberto. Inmunova S.a; Argentina. Fundación Instituto Leloir; Argentina
Fil: Zylberman, Vanesa. Inmunova S.a; Argentina. Fundación Instituto Leloir; Argentina
Fil: Palermo, Marina Sandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental; Argentina
Subject
Hemolytic Uremic Syndrome
SHIGA TOXIN 2
ANTI-STX2 ANTIBODIES
VACCINE
Biología Celular, Microbiología
Ciencias Biológicas
CIENCIAS NATURALES Y EXACTAS
Access level
Restricted access
License
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repository
CONICET Digital (CONICET)
Institution
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identifier
oai:ri.conicet.gov.ar:11336/7774