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Protective immunity against Clostridium difficile toxin A induced by oral immunization with a live, attenuated Vibrio cholerae vector strain.
Ryan, E T; Butterton, J R; Smith, R N; Carroll, P A; Crean, T I; Calderwood, S B.
Afiliação
  • Ryan ET; Infectious Disease Division, Massachusetts General Hospital, Boston 02114, USA.
Infect Immun ; 65(7): 2941-9, 1997 Jul.
Article em En | MEDLINE | ID: mdl-9199470
Clostridium difficile causes pseudomembranous colitis through the action of Rho-modifying proteins, toxins A and B. Antibodies directed against C. difficile toxin A prevent or limit C. difficile-induced colitis. We engineered plasmid pETR14, containing the hlyB and hlyD genes of the Escherichia coli hemolysin operon, to express a fusion protein containing 720 amino acid residues from the nontoxic, receptor-binding, carboxy terminus of C. difficile toxin A and the secretion signal of E. coli hemolysin A. We introduced pETR14 into Vibrio cholerae and found that the toxin A-HlyA fusion protein was secreted by a number of V. cholerae strains and recognized by both monoclonal and polyclonal anti-C. difficile toxin A antibodies. We introduced pETR14 into an attenuated V. cholerae strain, O395-NT, and inoculated rabbits orally with this construct. Colonization studies disclosed that the V. cholerae vector containing pETR14 was recoverable from rabbit ilea up to 5 days after oral inoculation. Vaccination produced significant systemic anti-C. difficile toxin A immunoglobulin G and anti-V. cholerae vibriocidal antibody responses. Vaccination also produced significant protection against toxin A in an ileal loop challenge assay, as assessed by determination of both fluid secretion and histological changes. These results suggest that the hemolysin system of E. coli can be used successfully in V. cholerae vector strains to effect secretion of large heterologous antigens and that a V. cholerae vector strain secreting a nontoxic, immunogenic portion of C. difficile toxin A fused to the secretion signal of E. coli HlyA induces protective systemic and mucosal immunity against this toxin.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Proteínas de Bactérias / Toxinas Bacterianas / Vibrio cholerae / Vacinas Bacterianas / Clostridioides difficile / Proteínas de Escherichia coli / Enterotoxinas / Vetores Genéticos / Proteínas Hemolisinas Limite: Animals Idioma: En Revista: Infect Immun Ano de publicação: 1997 Tipo de documento: Article País de afiliação: Estados Unidos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Proteínas de Bactérias / Toxinas Bacterianas / Vibrio cholerae / Vacinas Bacterianas / Clostridioides difficile / Proteínas de Escherichia coli / Enterotoxinas / Vetores Genéticos / Proteínas Hemolisinas Limite: Animals Idioma: En Revista: Infect Immun Ano de publicação: 1997 Tipo de documento: Article País de afiliação: Estados Unidos