Ghose Chandrabali, Eugenis Ioannis, Sun Xingmin, Edwards Adrianne N, McBride Shonna M, Pride David T, Kelly Ciarán P, Ho David D
Aaron Diamond AIDS Research Center, New York, NY 10075, USA.
Tufts University, Cummings School of Veterinary Medicine, North Grafton, MA 01536, USA.
Emerg Microbes Infect. 2016 Feb 3;5(2):e8. doi: 10.1038/emi.2016.8.
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.
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医院获得性腹泻的主要病因。艰难梭菌鞭毛在定植、黏附、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整体毒力。人和动物研究表明,抗鞭毛免疫反应可能在预防艰难梭菌定植和后续疾病结局中发挥作用。在此我们报告,重组艰难梭菌鞭毛蛋白(FliC)在艰难梭菌感染(CDI)小鼠模型中对临床艰难梭菌菌株UK1具有免疫原性和保护作用。在小鼠中使用抗FliC多克隆血清进行的被动保护实验表明这种保护是由抗体介导的。在用艰难梭菌630Δerm攻击后,FliC免疫也能够为仓鼠提供针对CDI和死亡的部分保护。此外,通过比较接种疫苗的仓鼠和对照仓鼠的粪便微生物群,证明针对FliC的免疫对接种疫苗的仓鼠的正常肠道菌群没有不利影响。因此,将FliC用作抗CDI疫苗候选物值得进一步测试。