Salmonella enterica Serovar Typhimurium Vaccine Strains Expressing a Nontoxic Shiga-Like Toxin 2 Derivative Induce Partial ProtectiveImmunity to the Toxin Expressed by Enterohemorrhagic Escherichia coli
Clinical vaccine immunology
; 17(4): 529-536, apr.2010.
Artigo
em Inglês
| Sec. Est. Saúde SP, SESSP-IBPROD, Sec. Est. Saúde SP, SESSP-IBACERVO
| ID: biblio-1062098
Biblioteca responsável:
BR78.1
Localização: BR78.1
ABSTRACT
Shiga-like toxin 2 (Stx2)-producing enterohemorrhagic Escherichia coli (referred to as EHEC or STEC) strainsare the primary etiologic agents of hemolytic-uremic syndrome (HUS), which leads to renal failure and highmortality rates. Expression of Stx2 is the most relevant virulence-associated factor of EHEC strains, and toxin neutralization by antigen-specific serum antibodies represents the main target for both preventive and therapeuticanti-HUS approaches. In the present report, we describe two Salmonella enterica serovar Typhimurium aroA vaccine strains expressing a nontoxic plasmid-encoded derivative of Stx2 (Stx2 AB) containing the complete nontoxic A2 subunit and the receptor binding B subunit. The two S. Typhimurium strains differ inthe expression of flagellin, the structural subunit of the flagellar shaft, which exerts strong adjuvant effects. Thevaccine strains expressed Stx2 AB, either cell bound or secreted into the extracellular environment, andshowed enhanced mouse gut colonization and high plasmid stability under both in vitro and in vivo conditions.Oral immunization of mice with three doses of the S. Typhimurium vaccine strains elicited serum anti-Stx2B(IgG) antibodies that neutralized the toxic effects of the native toxin under in vitro conditions (Vero cells) andconferred partial protection under in vivo conditions. No significant differences with respect to gut colonization or the induction of antigen-specific antibody responses were detected in mice vaccinated with flagellated versus nonflagellated bacterial strains. The present results indicate that expression of Stx2 AB by attenuated S. Typhimurium strains is an alternative vaccine approach for HUS control, but additional improvements in the immunogenicity of Stx2 toxoids are still required.
Texto completo:
Disponível
Coleções:
Bases de dados nacionais
/
Brasil
Contexto em Saúde:
Doenças Negligenciadas
Problema de saúde:
Doenças Negligenciadas
/
Zoonoses
Base de dados:
Sec. Est. Saúde SP
/
SESSP-IBACERVO
/
SESSP-IBPROD
Assunto principal:
Células Vero
/
Vacinas
/
Escherichia coli Enteropatogênica
Limite:
Animais
/
Humanos
Idioma:
Inglês
Revista:
Clinical vaccine immunology
Ano de publicação:
2010
Tipo de documento:
Artigo
Instituição/País de afiliação:
Instituto Butantan/BR