Active immunization of hamsters against Clostridium difficile infection using surface-layer protein
Active immunization of hamsters against Clostridium difficile infection using surface-layer protein
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DOI：
10.1111/j.1574-695x.2007.00363.x
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发表时间：
2008-03-01
影响因子：
--
通讯作者：
Kelleher, Dermot P.
中科院分区：
文献类型：
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作者：
Eidhin, Deirdre B. Ni;O'Brien, Julie B.;Kelleher, Dermot P.
艰难梭菌是感染性腹泻的主要原因，特别是在老年人中。其表面层蛋白（SLP）作为一种疫苗成分进行了测试，在一系列的免疫和攻击实验与金黄色叙利亚仓鼠，结合不同的全身和粘膜佐剂。还在非激发BALB/c小鼠模型中测试了一些方案，从而能够更密切地监测免疫应答。在仓鼠模型中，没有一种方案能提供完全的保护，抗体刺激在方案中是可变的，通常是适度的或差的。与仓鼠相比，小鼠对SLP表现出更强的抗体反应。5只给予SLP与Ribi（单磷酰脂质A和合成海藻糖dicornomycolate）的仓鼠中有2只在挑战中存活，3只给予SLP与Ribi和霍乱毒素的仓鼠中有2只存活。谨慎解释这种适度的保护趋势，因为幸存者的抗SLP血清抗体滴度较低。仓鼠是远交系，比近交系动物具有更多的遗传变异性;然而，BALB/c小鼠也显示出强烈的可变抗体应答。显然需要更好的佐剂用于单组分疫苗，特别是用于粘膜递送。仓鼠攻击模型可能需要修改，以用于SLP的主动免疫实验。
Clostridium difficile is the leading cause of infectious antibiotic-associated diarrhoea, particularly among the elderly. Its surface-layer protein (SLP) was tested as a vaccine component in a series of immunization and challenge experiments with Golden Syrian hamsters, combined with different systemic and mucosal adjuvants. Some regimens were also tested in a nonchallenge BALB/c mouse model, enabling closer monitoring of the immune response. None of the regimens conferred complete protection in the hamster model, and antibody stimulation was variable within regimens, and generally modest or poor. Mice displayed stronger antibody responses to SLP compared with hamsters. Two hamsters of five given SLP with Ribi (monophosphoryl lipid A and synthetic trehalose dicorynomycolate) survived the challenge, as did two of three given SLP with Ribi and cholera toxin. This modest trend to protection is interpreted with caution, because the survivors had low anti-SLP serum antibody titres. The hamsters were an outbred line, and subject to more genetic variability than inbred animals; however, BALB/c mice also showed strongly variable antibody responses. There is a clear need for better adjuvants for single-component vaccines, particularly for mucosal delivery. The hamster challenge model may need to be modified to be useful in active immunization experiments with SLP.