Immunogenicity and protective efficacy of recombinant Clostridium difficile flagellar protein FliC.
Immunogenicity and protective efficacy of recombinant Clostridium difficile flagellar protein FliC.
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DOI：
10.1038/emi.2016.8
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发表时间：
2016-02-03
影响因子：
13.2
通讯作者：
Ho DD
中科院分区：
文献类型：
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作者：
Ghose C;Eugenis I;Sun X;Edwards AN;McBride SM;Pride DT;Kelly CP;Ho DD
艰难梭菌是一种革兰氏阳性杆菌，是抗生素使用后毒素介导的院内腹泻的主要原因。C.艰难梭菌鞭毛在定殖、粘附、生物膜形成和毒素产生中起作用，这可能有助于某些菌株的总体毒力。人类和动物研究表明，抗鞭毛免疫应答可能在保护免受C.艰难和随后的疾病结果。在这里，我们报告，重组C。艰难梭菌鞭毛蛋白（FliC）在C.艰难梭菌感染（CDI）对临床C.艰难梭菌菌株，UK1。在小鼠中使用抗FliC多克隆血清的被动保护实验表明这种保护是抗体介导的。FliC免疫还能够在用C. difficile 630Δ λ。此外，通过比较接种和对照仓鼠的粪便微生物组证明，针对FliC的免疫接种对接种仓鼠的正常肠道植物群没有不良影响。因此，使用FliC作为抗CDI的候选疫苗需要进一步测试。
Clostridium difficile is a Gram-positive bacillus and is the leading cause of toxin-mediated nosocomial diarrhea following antibiotic use. C. difficile flagella play a role in colonization, adherence, biofilm formation, and toxin production, which might contribute to the overall virulence of certain strains. Human and animal studies indicate that anti-flagella immune responses may play a role in protection against colonization by C. difficile and subsequent disease outcome. Here we report that recombinant C. difficile flagellin (FliC) is immunogenic and protective in a murine model of C. difficile infection (CDI) against a clinical C. difficile strain, UK1. Passive protection experiments using anti-FliC polyclonal serum in mice suggest this protection to be antibody-mediated. FliC immunization also was able to afford partial protection against CDI and death in hamsters following challenge with C. difficile 630Δerm. Additionally, immunization against FliC does not have an adverse effect on the normal gut flora of vaccinated hamsters as evidenced by comparing the fecal microbiome of vaccinated and control hamsters. Therefore, the use of FliC as a vaccine candidate against CDI warrants further testing.