van Diemen P M, Dziva F, Abu-Median A, Wallis T S, van den Bosch H, Dougan G, Chanter N, Frankel G, Stevens M P
Institute for Animal Health, Compton, Berkshire RG20 7NN, UK.
Vet Immunol Immunopathol. 2007 Mar 15;116(1-2):47-58. doi: 10.1016/j.vetimm.2006.12.009. Epub 2007 Jan 9.
Enterohaemorrhagic Escherichia coli (EHEC) infections in humans are an important public health concern and are commonly acquired via contact with ruminant faeces. Cattle are a key control point however cross-protective vaccines for the control of EHEC in the bovine reservoir do not yet exist. The EHEC serogroups that are predominantly associated with human infection in Europe and North America are O157 and O26. Intimin and EHEC factor for adherence (Efa-1) play important roles in intestinal colonisation of cattle by EHEC and are thus attractive candidates for the development of subunit vaccines. Immunisation of calves with the cell-binding domain of intimin subtypes beta or gamma via the intramuscular route induced antigen-specific serum IgG1 and, in some cases salivary IgA responses, but did not reduce the magnitude or duration of faecal excretion of EHEC O26:H- (Int(280)-beta) or EHEC O157:H7 (Int(280)-gamma) upon subsequent experimental challenge. Similarly, immunisation of calves via the intramuscular route with the truncated Efa-1 protein (Efa-1') from EHEC O157:H7 or a mixture of the amino-terminal and central thirds of the full-length protein (Efa-1-N and M) did not protect against intestinal colonisation by EHEC O157:H7 (Efa-1') or EHEC O26:H- (Efa-1-N and M) despite the induction of humoral immunity. A portion of the serum IgG1 elicited by the truncated recombinant antigens in calves was confirmed to recognise native protein exposed on the bacterial surface. Calves immunised with a mixture of Int(280)-gamma and Efa-1' or an EHEC O157:H7 bacterin via the intramuscular route then boosted via the intranasal route with the same antigens using cholera toxin B subunit as an adjuvant were also not protected against intestinal colonisation by EHEC O157:H7. These studies highlight the need for further studies to develop and test novel vaccines or treatments for control of this important foodborne pathogen.
人感染肠出血性大肠杆菌(EHEC)是一个重要的公共卫生问题,通常通过接触反刍动物粪便而感染。牛是关键控制点,但目前尚无用于控制牛群中EHEC的交叉保护疫苗。在欧洲和北美,主要与人类感染相关的EHEC血清型是O157和O26。紧密素和EHEC黏附因子(Efa-1)在EHEC对牛肠道的定殖中起重要作用,因此是亚单位疫苗开发的有吸引力的候选物。通过肌肉途径用紧密素亚型β或γ的细胞结合域免疫犊牛,可诱导抗原特异性血清IgG1,在某些情况下还可诱导唾液IgA反应,但在随后的实验性攻毒后,并未减少EHEC O26:H-(Int(280)-β)或EHEC O157:H7(Int(280)-γ)粪便排泄的量或持续时间。同样,通过肌肉途径用来自EHEC O157:H7的截短Efa-1蛋白(Efa-1')或全长蛋白的氨基末端和中央三分之一的混合物(Efa-1-N和M)免疫犊牛,尽管诱导了体液免疫,但并不能预防EHEC O157:H7(Efa-1')或EHEC O26:H-(Efa-1-N和M)对肠道的定殖。犊牛中截短的重组抗原诱导产生的一部分血清IgG1被证实可识别细菌表面暴露的天然蛋白。通过肌肉途径用Int(280)-γ和Efa-1'的混合物或EHEC O157:H7菌苗免疫犊牛,然后使用霍乱毒素B亚单位作为佐剂通过鼻内途径用相同抗原进行加强免疫,也不能预防EHEC O157:H7对肠道的定殖。这些研究突出表明,需要进一步开展研究,以开发和测试用于控制这种重要食源性病原体的新型疫苗或治疗方法。