Fimbriae mediate the initial adherence of enterotoxigenic Escherichia coli (ETEC) to the piglet small intestine and play an important role in development of ETEC-driven postweaning diarrhea (PWD). PWD inflicts huge economic losses on the swine industry each year, making development of alternative treatment and prevention measures for PWD essential. Vaccine candidates that induce antifimbria antibodies that block the initial attachment and colonization of ETEC pathogens with fimbriae are one approach that could help prevent PWD. In this study, we constructed two multiepitope fusion antigens (MEFAs) that carried, expressed, and displayed representative epitopes of F4, F5, F6, F18, and F41 ETEC fimbriae. These MEFAs used either the F4 major subunit FaeG or the F18 adhesive subunit FedF as a backbone. To assess the potential of these MEFAs as antifimbria vaccine candidates that could help prevent PWD, we generated computational models of the MEFAs, constructed them, and then tested their immunogenicity by using them to immunize mice. Computational modeling showed that all relevant epitopes were exposed on the MEFA surface. We found that coadministration of our MEFAs in mice successfully induced five fimbria-specific antibodies in accordance with the epitopes included in the MEFA constructs. Furthermore, the induced antibodies can significantly inhibit the ability of ETEC strains that express F4, F5, F6, F18, and F41 fimbriae to adhere to piglet small intestinal IPEC-1 and IPEC-J2 cells. Our findings indicate that the antifimbria antibodies induced by our FaeG-Fim41a-FanC-FasA and FedF-FasA-Fim41a-FanC fimbria MEFAs blocked adherence of five ETEC fimbriae, suggesting these multivalent fimbria MEFAs may be useful for developing broadly protective antifimbria vaccines against PWD caused by ETEC infections.

中文翻译：

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与两种肠毒素大肠杆菌（ETEC）纤维多表位融合抗原的共免疫诱导针对五种ETEC菌毛（F4，F5，F6，F18和F41）的中和抗体的产生

菌毛介导了产肠毒素大肠杆菌的初始黏附（ETEC）致仔猪小肠，并在ETEC驱动的断奶后腹泻（PWD）的发生中发挥重要作用。每年，残疾人都会给养猪业造成巨大的经济损失，因此必须开发替代治疗和预防措施。诱导抗菌毛抗体的疫苗候选物可以阻止菌毛的ETEC病原体的初始附着和定殖，这是一种有助于预防PWD的方法。在这项研究中，我们构建了两个多表位融合抗原（MEFA），它们携带，表达和展示F4，F5，F6，F18和F41 ETEC菌毛的代表性表位。这些MEFA使用F4主要亚基FaeG或F18粘性亚基FedF作为骨架。为了评估这些MEFA作为候选抗纤毛疫苗的潜力，可以帮助预防PWD，我们生成了MEFA的计算模型，构建了它们，然后通过使用它们免疫小鼠来测试其免疫原性。计算模型表明，所有相关的表位都暴露在MEFA表面上。我们发现，根据MEFA构建体中包含的表位，在小鼠中共同施用我们的MEFA成功诱导了五种菌毛特异性抗体。此外，诱导的抗体可以显着抑制表达F4，F5，F6，F18和F41菌毛的ETEC菌株粘附于仔猪小肠IPEC-1和IPEC-J2细胞的能力。我们的发现表明，我们的FaeG-Fim41a-FanC-FasA和FedF-FasA-Fim41a-FanC菌毛MEFA诱导的抗菌毛抗体会阻止5种ETEC菌毛的粘附，