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To develop a cross-protective\n            <jats:italic>Shigella<\/jats:italic>\n            vaccine, in this study, we constructed a polyvalent protein immunogen to present conserved immunodominant epitopes of\n            <jats:italic>Shigella<\/jats:italic>\n            invasion plasmid antigens B (IpaB) and D (IpaD), VirG, GuaB, and Shiga toxins on backbone protein IpaD, by applying an epitope- and structure-based multiepitope-fusion-antigen (MEFA) vaccinology platform, examined protein (\n            <jats:italic>Shigella<\/jats:italic>\n            MEFA) broad immunogenicity, and evaluated antibody function against\n            <jats:italic>Shigella<\/jats:italic>\n            invasion and Shiga toxin cytotoxicity but also protection against\n            <jats:italic>Shigella<\/jats:italic>\n            lethal challenge. Mice intramuscularly immunized with\n            <jats:italic>Shigella<\/jats:italic>\n            MEFA protein developed IgG responses to IpaB, IpaD, VirG, GuaB, and Shiga toxins 1 and 2; mouse sera significantly reduced invasion of\n            <jats:italic>Shigella sonnei<\/jats:italic>\n            ,\n            <jats:italic>Shigella flexneri<\/jats:italic>\n            serotype 2a, 3a, or 6,\n            <jats:italic>Shigella boydii,<\/jats:italic>\n            and\n            <jats:italic>Shigella dysenteriae<\/jats:italic>\n            type 1 and neutralized cytotoxicity of Shiga toxins of\n            <jats:italic>Shigella<\/jats:italic>\n            and Shiga toxin-producing\n            <jats:italic>Escherichia coli in vitro<\/jats:italic>\n            . Moreover, mice intranasally immunized with\n            <jats:italic>Shigella<\/jats:italic>\n            MEFA protein (adjuvanted with dmLT) developed antigen-specific serum IgG, lung IgG and IgA, and fecal IgA antibodies, and survived from lethal pulmonary challenge with\n            <jats:italic>S. sonnei<\/jats:italic>\n            or\n            <jats:italic>S. flexneri<\/jats:italic>\n            serotype 2a, 3a, or 6. In contrast, the control mice died, became unresponsive, or lost 20% of body weight in 48 h. These results indicated that this\n            <jats:italic>Shigella<\/jats:italic>\n            MEFA protein is broadly immunogenic, induces broadly functional antibodies, and cross-protects against lethal pulmonary challenges with\n            <jats:italic>S. sonnei<\/jats:italic>\n            or\n            <jats:italic>S. flexneri<\/jats:italic>\n            serotypes, suggesting a potential application of this polyvalent MEFA protein in\n            <jats:italic>Shigella<\/jats:italic>\n            vaccine development.\n          <\/jats:p>","DOI":"10.1128\/iai.00316-23","type":"journal-article","created":{"date-parts":[[2023,10,5]],"date-time":"2023-10-05T13:02:16Z","timestamp":1696510936000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":16,"title":["A broadly immunogenic polyvalent\n            <i>Shigella<\/i>\n            multiepitope fusion antigen protein protects against\n            <i>Shigella sonnei<\/i>\n            and\n            <i>Shigella flexneri<\/i>\n            lethal pulmonary challenges in mice"],"prefix":"10.1128","volume":"91","author":[{"given":"Siqi","family":"Li","sequence":"first","affiliation":[{"name":"Department of Pathobiology, University of Illinois at Urbana-Champaign , Urbana, Illinois, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaghayegh","family":"Anvari","sequence":"additional","affiliation":[{"name":"Department of Diagnostic Medicine\/Pathobiology, Kansas State University College of Veterinary Medicine , Manhattan, Kansas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Galen","family":"Ptacek","sequence":"additional","affiliation":[{"name":"Department of Pathobiology, University of Illinois at Urbana-Champaign , Urbana, Illinois, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ipshita","family":"Upadhyay","sequence":"additional","affiliation":[{"name":"Department of Pathobiology, University of Illinois at Urbana-Champaign , Urbana, Illinois, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4015-5694","authenticated-orcid":true,"given":"Robert W.","family":"Kaminski","sequence":"additional","affiliation":[{"name":"Department of Enteric Infections, Walter Reed Army Institute of Research , Silver Spring, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David A.","family":"Sack","sequence":"additional","affiliation":[{"name":"Department of International Health, Johns Hopkins University Bloomberg School of Public Health , Baltimore, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3723-2257","authenticated-orcid":true,"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"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(12)61728-0"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(14)61682-2"},{"key":"e_1_3_3_4_2","first-page":"1459","article-title":"Global, regional, and national incidence, prevalence, and years lived with disability for 310 diseases and injuries, 1990-2015: a systematic analysis for the global burden of disease study 2015","volume":"388","author":"Collaborators GMaCoD","year":"2016","unstructured":"Collaborators GMaCoD . 2016. 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