Title |
Recombinant lipoprotein-based vaccine candidates against C. difficile infections
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Published in |
Journal of Biomedical Science, August 2015
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DOI | 10.1186/s12929-015-0171-x |
Pubmed ID | |
Authors |
Jui-Hsin Huang, Chia-Wei Wu, Shu-Pei Lien, Chih-Hsiang Leng, Kuang-Nan Hsiao, Shih-Jen Liu, Hsin-Wei Chen, Leung-Kei Siu, Pele Chong |
Abstract |
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. 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. These results indicate that rlipoA-RBD formulated with B-rRBD could be an excellent vaccine candidate for preclinical studies and future clinical trials. |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Unknown | 33 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Ph. D. Student | 9 | 27% |
Student > Master | 4 | 12% |
Student > Doctoral Student | 2 | 6% |
Student > Bachelor | 2 | 6% |
Professor > Associate Professor | 2 | 6% |
Other | 6 | 18% |
Unknown | 8 | 24% |
Readers by discipline | Count | As % |
---|---|---|
Biochemistry, Genetics and Molecular Biology | 7 | 21% |
Agricultural and Biological Sciences | 5 | 15% |
Immunology and Microbiology | 5 | 15% |
Chemistry | 2 | 6% |
Medicine and Dentistry | 2 | 6% |
Other | 4 | 12% |
Unknown | 8 | 24% |