A DNA Vaccine Encoding the Enterohemorragic Escherichia coli Shiga-Like Toxin 2 A(2) and B Subunits Confers Protective Immunity to Shiga Toxin Challenge in the Murine Model


Autoria(s): BENTANCOR, Leticia V.; BILEN, Marcos; BRANDO, Romina J. Fernandez; RAMOS, Maria Victoria; FERREIRA, Luis C. S.; GHIRINGHELLI, Pablo D.; PALERMO, Marina S.
Contribuinte(s)

UNIVERSIDADE DE SÃO PAULO

Data(s)

20/10/2012

20/10/2012

2009

Resumo

Production of verocytotoxin or Shiga-like toxin (Stx), particularly Stx2, is the basis of hemolytic uremic syndrome, a frequently lethal outcome for subjects infected with Stx2-producing enterohemorrhagic Escherichia coli (EHEC) strains. The toxin is formed by a single A subunit, which promotes protein synthesis inhibition in eukaryotic cells, and five B subunits, which bind to globotriaosylceramide at the surface of host cells. Host enzymes cleave the A subunit into the A(1) peptide, endowed with N-glycosidase activity to the 28S rRNA, and the A(2) peptide, which confers stability to the B pentamer. We report the construction of a DNA vaccine (pStx2 Delta AB) that expresses a nontoxic Stx2 mutated form consisting of the last 32 amino acids of the A(2) sequence and the complete B subunit as two nonfused polypeptides. Immunization trials carried out with the DNA vaccine in BALB/c mice, alone or in combination with another DNA vaccine encoding granulocyte-macrophage colony-stimulating factor, resulted in systemic Stx-specific antibody responses targeting both A and B subunits of the native Stx2. Moreover, anti-Stx2 antibodies raised in mice immunized with pStx2 Delta AB showed toxin neutralization activity in vitro and, more importantly, conferred partial protection to Stx2 challenge in vivo. The present vector represents the second DNA vaccine so far reported to induce protective immunity to Stx2 and may contribute, either alone or in combination with other procedures, to the development of prophylactic or therapeutic interventions aiming to ameliorate EHEC infection-associated sequelae.

Fundacion Alberto J. Roemmers

Fundacion Alberto J. Roemmers

Consejo Nacional de Investigaciones Cientificas y Tecnologicas (CONICET)

Consejo Nacional de Investigaciones Científicas y Técnicas de Argentina (CONICET)

ANPCyT Agencia Nacional de Promocion Cientifica y Tecnologica, Argentina

Agencia Nacional de Promoción Científica y Tecnológica (ANPCyT)

Identificador

CLINICAL AND VACCINE IMMUNOLOGY, v.16, n.5, p.712-718, 2009

1556-6811

http://producao.usp.br/handle/BDPI/28464

10.1128/CVI.00328-08

http://dx.doi.org/10.1128/CVI.00328-08

Idioma(s)

eng

Publicador

AMER SOC MICROBIOLOGY

Relação

Clinical and Vaccine Immunology

Direitos

restrictedAccess

Copyright AMER SOC MICROBIOLOGY

Palavras-Chave #HEMOLYTIC-UREMIC SYNDROME #MONOCLONAL-ANTIBODIES #EDEMA DISEASE #INFECTION #MICE #IMMUNIZATION #VARIANTS #STRAINS #MUTANT #EPIDEMIOLOGY #Immunology #Infectious Diseases #Microbiology
Tipo

article

original article

publishedVersion