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Transcutaneous Immunization with Clostridium difficile Toxoid A Induces Systemic and Mucosal Immune Responses and Toxin A-Neutralizing Antibodies in Mice

机译:艰难梭菌类毒素A的经皮免疫诱导小鼠全身和粘膜的免疫反应和毒素A中和抗体。

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Clostridium difficile is the leading cause of nosocomial infectious diarrhea. C. difficile produces two toxins (A and B), and systemic and mucosal anti-toxin A antibodies prevent or limit C. difficile-associated diarrhea. To evaluate whether transcutaneous immunization with formalin-treated C. difficile toxin A (CDA) induces systemic and mucosal anti-CDA immune responses, we transcutaneously immunized three cohorts of mice with CDA with or without immunoadjuvantative cholera toxin (CT) on days 0, 14, 28, and 42. Mice transcutaneously immunized with CDA and CT developed prominent anti-CDA and anti-CT immunoglobulin G (IgG) and IgA responses in serum and anti-CDA and anti-CT IgA responses in stool. Sera from immunized mice were able to neutralize C. difficile toxin A activity in an in vitro cell culture assay. CDA itself demonstrated adjuvant activity and enhanced both serum and stool anti-CT IgA responses. Our results suggest that transcutaneous immunization with CDA toxoid may be a feasible immunization strategy against C. difficile, an important cause of morbidity and mortality against which current preventative strategies are failing.
机译:艰难梭菌是医院感染性腹泻的主要原因。 C。艰难梭菌产生两种毒素(A和B),全身和粘膜抗毒素A抗体可预防或限制C。难治性腹泻。评估是否用福尔马林处理过的 C进行经皮免疫。艰难梭菌毒素A(CDA)诱导全身和粘膜抗CDA免疫反应,我们在0、14、28和42天分别对3组患有CDA的小鼠(含或不含免疫佐剂霍乱毒素)进行了皮肤免疫。经CDA和CT透皮免疫后,血清中产生显着的抗CDA和抗CT免疫球蛋白G(IgG)和IgA反应,粪便中产生抗CDA和抗CT IgA反应。来自免疫小鼠的血清能够中和 C。体外细胞培养实验中发现艰难梭菌毒素A的活性。 CDA本身显示出佐剂活性,并增强了血清和粪便的抗CT IgA反应。我们的结果表明,CDA类毒素经皮免疫可能是针对 C的可行免疫策略。艰难梭状芽胞杆菌是发病率和死亡率的重要原因,目前的预防策略已无法解决。

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