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Protection of rabbits against enteropathogenic Escherichia coli (EPEC) using an intimin null mutant

机译:使用intimin null突变体保护家兔免受肠道致病性大肠杆菌(EPEC)

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Background Diarrhea and mortality resulting from infections with enteropathogenic Escherichia coli (EPEC) are of major economic importance in the rabbit meat industry. There is a growing need for an effective vaccine to cope with these problems and to reduce the use of antibiotics. EPEC are characterized by an attaching and effacing virulence mechanism. This is partly mediated by the intimate binding between an adhesin, called intimin, and a translocated receptor (Tir) of prokaryote origin. We constructed an intimin deletion mutant of the rabbit EPEC (REPEC) wild-type strain 97/241.6 (bio-/serogroup 3-/O15) and examined its protective capacity. Results After verifying its complete loss of virulence, we used the attenuated strain in vaccination-challenge experiments in which complete protection against a homologous, but virulent, strain was observed. The attenuated strain was able to persist in the intestinal lumen, where it elicited an immune response against EPEC-related virulence proteins, as was shown using an EspB-specific ELISA. Despite the priming of an immune response and the generation of specific antibodies, the intimin mutant was not able to fully protect rabbits against challenges with REPEC strains of other bio-/serogroups. Conclusion These data indicate that protection against REPEC infections is at least partly bio-/serogroup dependent and a multivalent vaccine may be needed for protection against the full range of REPEC types. Such a combination vaccine may be developed using intimin null mutants, as the latter were clearly shown to be safe and effective against homologous infections.
机译:背景技术由肠致病性大肠杆菌(EPEC)感染引起的腹泻和死亡率在兔肉工业中具有重要的经济意义。人们日益需要一种有效的疫苗来应对这些问题并减少抗生素的使用。 EPEC的特征在于附着和消失的毒力机制。这部分是由称为内膜蛋白的粘附素与原核生物起源的易位受体(Tir)之间的紧密结合介导的。我们构建了兔EPEC(REPEC)野生型菌株97 / 241.6(bio- / serogroup 3- / O15)的intimin缺失突变体,并研究了其保护能力。结果在确认其完全丧失毒力后,我们在疫苗接种挑战实验中使用了减毒株,其中观察到了针对同源但有毒力株的完全保护。减毒菌株能够在肠道内腔中持续存在,并引起针对EPEC相关毒力蛋白的免疫反应,如EspB特异性ELISA所示。尽管引发了免疫反应并产生了特异性抗体,intimin突变体仍不能完全保护兔子免受其他生物/血清群的REPEC菌株的攻击。结论这些数据表明,针对REPEC感染的防护至少部分取决于生物/血清群,并且可能需要多价疫苗来针对所有REPEC类型的疫苗进行防护。这样的联合疫苗可以使用intimin null突变体开发,因为intimin null突变体已明确显示出对同源感染是安全有效的。

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