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Vaccination is considered to be the most ideal and efficacious strategy for preventing PWD. Recently, a commercialized live monovalent F4 oral vaccine and a bivalent F4\/F18 oral vaccine have been demonstrated to effectively protect piglets in the F4-positive (F4<jats:sup>+<\/jats:sup>) and F18<jats:sup>+<\/jats:sup>ETEC challenge models. However, they will not provide cross-protection against F5<jats:sup>+<\/jats:sup>, F6<jats:sup>+<\/jats:sup>, or F41<jats:sup>+<\/jats:sup>ETEC-associated PWD cases, as they lack all five fimbria antigens. Thus, a multivalent vaccine containing all five ETEC fimbriae would be more effective in preventing ETEC-driven PWD. In this study, we designed two fimbria-targeted MEFAs using the MEFA technology, and further study demonstrated that these coadministered MEFAs in mice can induce protective antibodies against the five fimbriae expressed by ETEC. These MEFAs could be used as an efficient PWD vaccine candidate; furthermore, MEFA-based structural technology provides an alternative and promising strategy for the development of vaccines against pathogens with heterogeneous virulence factors.<\/jats:p>","DOI":"10.1128\/aem.00217-20","type":"journal-article","created":{"date-parts":[[2020,3,11]],"date-time":"2020-03-11T10:23:17Z","timestamp":1583922197000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":19,"title":["Coimmunization with Two Enterotoxigenic Escherichia coli (ETEC) Fimbrial Multiepitope Fusion Antigens Induces the Production of Neutralizing Antibodies against Five ETEC Fimbriae (F4, F5, F6, F18, and F41)"],"prefix":"10.1128","volume":"86","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6934-9142","authenticated-orcid":false,"given":"Qiangde","family":"Duan","sequence":"first","affiliation":[{"name":"College of Veterinary Medicine (Institute of Comparative Medicine), Yangzhou University, Yangzhou, China"},{"name":"Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Joint International Research Laboratory of Agriculture and Agri-Product Safety, Ministry of Education of China, Yangzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenwen","family":"Wu","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine (Institute of Comparative Medicine), Yangzhou University, Yangzhou, China"},{"name":"Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Joint International Research Laboratory of Agriculture and Agri-Product Safety, Ministry of Education of China, Yangzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shengmei","family":"Pang","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine (Institute of Comparative Medicine), Yangzhou University, Yangzhou, China"},{"name":"Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Joint International Research Laboratory of Agriculture and Agri-Product Safety, Ministry of Education of China, Yangzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiming","family":"Pan","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine (Institute of Comparative Medicine), Yangzhou University, Yangzhou, China"},{"name":"Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Joint International Research Laboratory of Agriculture and Agri-Product Safety, Ministry of Education of China, Yangzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3723-2257","authenticated-orcid":false,"given":"Weiping","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pathobiology, University of Illinois at Urbana-Champaign, Urbana, Illinois, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guoqiang","family":"Zhu","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine (Institute of Comparative Medicine), Yangzhou University, Yangzhou, China"},{"name":"Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Joint International Research Laboratory of Agriculture and Agri-Product Safety, Ministry of Education of China, Yangzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1079\/ahr2005105"},{"key":"e_1_3_2_3_2","first-page":"259","article-title":"Enterotoxigenic Escherichia coli (ETEC) in farm animals","volume":"30","author":"Nagy B","year":"1999","unstructured":"Nagy B, Fekete PZ. 1999. 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