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Recombinant lipoprotein-based vaccine candidates against C. difficile infections
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نویسنده
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huang j.-h. ,wu c.-w. ,lien s.-p. ,leng c.-h. ,hsiao k.-n. ,liu s.-j. ,chen h.-w. ,siu l.-k. ,chong p.
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منبع
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journal of biomedical science - 2015 - دوره : 22 - شماره : 1
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چکیده
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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. © 2015 huang et al.
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کلیدواژه
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Adjuvant; Antibiotic-associated pseudo-membranous colitis; C. difficile toxins; Lipoprotein; Receptor binding domain; Toll-like receptor agonist
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آدرس
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vaccine r and d center,national institute of infectious diseases and vaccinology,national health research institutes,zhunan town,miaoli county,taiwan,graduate institute of life science,national defense medical centertaipei, Taiwan, vaccine r and d center,national institute of infectious diseases and vaccinology,national health research institutes,zhunan town,miaoli county, Taiwan, vaccine r and d center,national institute of infectious diseases and vaccinology,national health research institutes,zhunan town,miaoli county, Taiwan, vaccine r and d center,national institute of infectious diseases and vaccinology,national health research institutes,zhunan town,miaoli county, Taiwan, vaccine r and d center,national institute of infectious diseases and vaccinology,national health research institutes,zhunan town,miaoli county, Taiwan, vaccine r and d center,national institute of infectious diseases and vaccinology,national health research institutes,zhunan town,miaoli county, Taiwan, vaccine r and d center,national institute of infectious diseases and vaccinology,national health research institutes,zhunan town,miaoli county, Taiwan, vaccine r and d center,national institute of infectious diseases and vaccinology,national health research institutes,zhunan town,miaoli county, Taiwan, vaccine r and d center,national institute of infectious diseases and vaccinology,national health research institutes,zhunan town,miaoli county,taiwan,graduate institute of life science,national defense medical centertaipei,taiwan,graduate institute of immunology,china medical university,taichung, Taiwan
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Authors
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