Colonisation Factor CD0873, an Attractive Oral Vaccine Candidate against Clostridioides difficile.
Colonisation Factor CD0873, an Attractive Oral Vaccine Candidate against Clostridioides difficile.
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DOI：
10.3390/microorganisms9020306
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发表时间：
2021-02-02
期刊：
影响因子：
4.5
通讯作者：
Griffin R
中科院分区：
文献类型：
--
作者：
Karyal C;Hughes J;Kelly ML;Luckett JC;Kaye PV;Cockayne A;Minton NP;Griffin R
艰难梭菌是卫生保健相关感染性腹泻的主要原因。由该细菌分泌的毒素TcdA和TcdB损害结肠上皮细胞，并且在严重的情况下，这最终导致伪膜性结肠炎、中毒性巨结肠和死亡。人体试验中的疫苗专门集中在基于毒素的制剂的肠胃外给药。这些疫苗促进毒素中和血清抗体，但不能保护肠道免受感染。口服途径是免疫肠道病原体并在感染部位刺激保护性粘膜抗体应答（分泌型免疫球蛋白A，伊加）的有效途径。此外，口服免疫产生全身性抗体（IgG）。使用这种途径，在仓鼠模型中测试了两种不同的抗原：定殖因子CD 0873和TcdB片段。与未接种过CD 0873的动物相比，用CD 0873免疫的动物在肠液中产生了显着更高的sIgA滴度，在血清中产生了显着更高的IgG滴度，这显着抑制了C.对Caco-2细胞来说很难。在用高毒力分离株攻毒后，与未经处理的动物相比，CD 0873免疫组显示出至实验终点的时间平均增加80%。存活率和身体状况与盲肠中的细菌清除和病理学减少相关。我们的研究结果表明，CD 0873是一种有希望的抗C.很难
Clostridioides difficile is the main cause of health-care-associated infectious diarrhoea. Toxins, TcdA and TcdB, secreted by this bacterium damage colonic epithelial cells and in severe cases this culminates in pseudomembranous colitis, toxic megacolon and death. Vaccines in human trials have focused exclusively on the parenteral administration of toxin-based formulations. These vaccines promote toxin-neutralising serum antibodies but fail to confer protection from infection in the gut. An effective route to immunise against gut pathogens and stimulate a protective mucosal antibody response (secretory immunoglobulin A, IgA) at the infection site is the oral route. Additionally, oral immunisation generates systemic antibodies (IgG). Using this route, two different antigens were tested in the hamster model: The colonisation factor CD0873 and a TcdB fragment. Animals immunised with CD0873 generated a significantly higher titre of sIgA in intestinal fluid and IgG in serum compared to naive animals, which significantly inhibited the adherence of C. difficile to Caco-2 cells. Following challenge with a hypervirulent isolate, the CD0873-immunised group showed a mean increase of 80% in time to experimental endpoint compared to naïve animals. Survival and body condition correlated with bacterial clearance and reduced pathology in the cecum. Our findings advocate CD0873 as a promising oral vaccine candidate against C. difficile.
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