Serum antitoxin antibodies mediate systemic and mucosal protection from Clostridium difficile disease in hamsters
Serum antitoxin antibodies mediate systemic and mucosal protection from Clostridium difficile disease in hamsters
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DOI：
10.1128/iai.67.2.527-538.1999
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发表时间：
1999-02-01
影响因子：
3.1
通讯作者：
Thomas, WD
中科院分区：
文献类型：
--
作者：
Giannasca, PJ;Zhang, ZX;Thomas, WD
艰难梭菌是被鉴定为伪膜性结肠炎的原因的细菌病原体，并且是医院内腹泻相关性腹泻和结肠炎的主要原因。与这种感染相关的病理学发现被认为是由两种大的（类似于300-kDa）外毒素，毒素A和B引起的。由于这种感染的粘膜性质，旨在提供预防性或治疗性免疫保护的疫苗接种策略包括通过粘膜途径免疫。利用C.艰难梭菌感染，我们检查了灭活毒素（类毒素）疫苗制剂的保护效力，所述灭活毒素（类毒素）疫苗制剂制备为培养物滤液或部分纯化的环状物。我们比较了包括鼻内、胃内或直肠免疫途径的胃肠外和粘膜联合疫苗接种方案，发现直肠免疫与肌内（i.m.）接种提供了完全保护仓鼠免于死亡和腹泻，而其他粘膜途径则没有。保护与血清中高水平的毒素中和抗体有关。通过使用连续i.m.直肠或肌内注射疫苗接种方案。没想到，M。没有佐剂的免疫给予了最高的免于死亡和腹泻的保护;该方案引起了最高的血清抗毒素B滴度以及毒素B中和滴度。被动转移小鼠抗毒素抗体以剂量依赖性方式保护仓鼠，证明循环抗毒素抗体在这种毒素介导的粘膜疾病的免疫中的主要作用。这些结果表明，预防性胃肠外疫苗接种或静脉免疫治疗可以提供保护，从C。人类的艰难梭菌病
Clostridium difficile is the bacterial pathogen identified as the cause of pseudomembranous colitis and is principally responsible for nosocomial antibiotic-associated diarrhea and colitis. The pathologic findings associated with this infection are believed to be caused by two large (similar to 300-kDa) exotoxins, toxins A and B. Because of the mucosal nature of this infection, vaccination strategies aimed at providing prophylactic or therapeutic immune protection have included immunization by mucosal routes. Using the hamster model of C. difficile infection, we examined the protective efficacy of inactivated toxin (toxoid) vaccine formulations prepared as either culture filtrate or partially purified toroid. We compared combination parenteral and mucosal vaccination regimens involving intranasal, intragastric, or rectal routes of immunization and found that rectal immunization in conjunction with intramuscular (i.m.) vaccination provided full protection of hamsters from death and diarrhea while the other mucosal routes did not. Protection was associated with high levels of toxin-neutralizing antibodies in serum. The requirement for adjuvants for protection was assessed by using sequential i.m. and rectal or i.m. vaccination regimens. Unexpectedly, i.m. immunization without adjuvant conferred the highest protection from death and diarrhea; this regimen elicited the highest serum anti-toxin B titers as well as toxin B neutralizing titers. Passive transfer of mouse antitoxin antibodies protected hamsters in a dose-dependent manner, demonstrating the principal role of circulating antitoxin antibodies in immunity from this toxin-mediated mucosal disease. These results suggest that prophylactic parenteral vaccination or intravenous immunotherapy could provide protection from C. difficile disease in humans.