Recombinant lipoprotein-based vaccine candidates against C. difficile infections.
J Biomed Sci
; 22: 65, 2015 Aug 07.
Article
em En
| MEDLINE
| ID: mdl-26245825
ABSTRACT
BACKGROUND:
Opportunistically nosocomial infections in hospitalized patients are often related to Clostridium difficile infections (CDI) due to disruption of the intestinal micro-flora by antibiotic therapies during hospitalization. Clostridial exotoxins A and B (TcdA and TcdB) specifically bind to unknown glycoprotein(s) in the host intestine, disrupt the intestinal barrier leading to acute inflammation and diarrhea. The C-terminal receptor binding domain of TcdA (A-rRBD) has been shown to elicit antibody responses that neutralize TcdA toxicity in Vero cell cytotoxicity assays, but not effectively protect hamsters against a lethal dose challenge of C. difficile spores. To develop an effective recombinant subunit vaccine against CDI, A-rRBD was lipidated (rlipoA-RBD) as a rational design to contain an intrinsic adjuvant, a toll-like receptor 2 agonist and expressed in Escherichia coli.RESULTS:
The purified rlipoA-RBD was characterized immunologically and found to have the following properties (a) mice, hamsters and rabbits vaccinated with 3 µg of rlipoA-RBD produced strong antibody responses that neutralized TcdA toxicity in Vero cell cytotoxicity assays; furthermore, the neutralization titer was comparable to those obtained from antisera immunized either with 10 µg of TcdA toxoid or 30 µg of A-rRBD; (b) rlipoA-RBD elicited immune responses and protected mice from TcdA challenge, but offered insignificant protection (10 to 20 %) against C. difficile spores challenge in hamster models; (c) only rlipoA-RBD formulated with B-rRBD consistently confers protection (90 to 100 %) in the hamster challenge model; and (d) rlipoA-RBD was found to be 10-fold more potent than A-rRBD as an adjuvant to enhancing immune responses against a poor antigen such as ovalbumin.CONCLUSION:
These results indicate that rlipoA-RBD formulated with B-rRBD could be an excellent vaccine candidate for preclinical studies and future clinical trials.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Enterocolite Pseudomembranosa
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Vacinas Bacterianas
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Clostridioides difficile
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Lipoproteínas
Limite:
Animals
Idioma:
En
Revista:
J Biomed Sci
Assunto da revista:
MEDICINA
Ano de publicação:
2015
Tipo de documento:
Article
País de afiliação:
Taiwan