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Virulence heterogeneity is a key obstacle to developing vaccines against\n                      <jats:italic toggle=\"yes\">Shigella<\/jats:italic>\n                      or ETEC. By applying a multiepitope fusion antigen (MEFA) vaccinology platform, we recently constructed epitope- and structure-based polyvalent proteins to induce cross-protective antibodies against heterogeneous\n                      <jats:italic toggle=\"yes\">Shigella<\/jats:italic>\n                      or ETEC strains. In this study, we combined a polyvalent\n                      <jats:italic toggle=\"yes\">Shigella<\/jats:italic>\n                      protein with two polyvalent ETEC proteins, examined antigen compatibility and broad immunogenicity, and evaluated the potential of developing a combined vaccine against the two groups of bacteria. Data showed that mice intramuscularly immunized with the combined vaccine candidate (ShecVax) developed antibodies to all the following target virulence factors:\n                      <jats:italic toggle=\"yes\">Shigella<\/jats:italic>\n                      IpaB, IpaD, VirG, GuaB, StxA, Stx2A, and StxB, and ETEC STa, LT, CFA\/I, CS1, CS2, CS3, CS4, CS5, and CS6. ShecVax-induced antibodies significantly inhibited the invasion of all\n                      <jats:italic toggle=\"yes\">Shigella<\/jats:italic>\n                      species and important serotypes, prevented the adherence of all important ETEC pathotypes, and neutralized the enterotoxicity of ETEC toxins STa and LT. Moreover, ShecVax prevented mice from lethal pulmonary infection with\n                      <jats:italic toggle=\"yes\">Shigella sonnei<\/jats:italic>\n                      or\n                      <jats:italic toggle=\"yes\">S. flexneri<\/jats:italic>\n                      2a, significantly reduced ETEC bacterial colonization in rabbit small intestines, and passively protected newborn pigs against ETEC toxin-mediated clinical diarrhea. These results indicated that ShecVax is broadly immunogenic and cross-protective against\n                      <jats:italic toggle=\"yes\">Shigella<\/jats:italic>\n                      and ETEC, suggesting ShecVax can be a\n                      <jats:italic toggle=\"yes\">Shigella<\/jats:italic>\n                      \/ETEC combined vaccine against children\u2019s and travelers\u2019 diarrhea, and the MEFA platform can be generally applied for vaccine development against heterogeneous pathogens or different diseases.\n                    <\/jats:p>\n                    <jats:sec>\n                      <jats:title>IMPORTANCE<\/jats:title>\n                      <jats:p>\n                        There are no effective countermeasures against\n                        <jats:italic toggle=\"yes\">Shigella<\/jats:italic>\n                        and enterotoxigenic\n                        <jats:italic toggle=\"yes\">E. coli<\/jats:italic>\n                        (ETEC), two antibiotic-resistant groups of bacteria and the leading causes of diarrhea in children in developing countries (children\u2019s diarrhea) and international travelers (travelers\u2019 diarrhea). Vaccines are a more practical approach to protect against infectious diseases, including diarrhea caused by\n                        <jats:italic toggle=\"yes\">Shigella<\/jats:italic>\n                        or ETEC. A combined vaccine cross-protective against\n                        <jats:italic toggle=\"yes\">Shigella<\/jats:italic>\n                        and ETEC can save hundreds of thousands of lives and prevent hundreds of millions of diarrhea cases yearly; it can also reduce antibiotic prescription and decrease antibiotic resistance, thus significantly improving global health. In addition, we may apply the MEFA platform to develop combined vaccines against heterogeneous pathogens or different diseases to accommodate an increasingly crowded expanded program on immunization (EPI).\n                      <\/jats:p>\n                    <\/jats:sec>\n                  <\/jats:sec>","DOI":"10.1128\/iai.00004-25","type":"journal-article","created":{"date-parts":[[2025,4,10]],"date-time":"2025-04-10T09:45:08Z","timestamp":1744278308000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":9,"title":["Immunogenicity and preclinical efficacy characterization of ShecVax, a combined vaccine against\n                    <i>Shigella<\/i>\n                    and enterotoxigenic\n                    <i>Escherichia coli<\/i>"],"prefix":"10.1128","volume":"93","author":[{"given":"Siqi","family":"Li","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/047426m28","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Pathobiology, University of Illinois at Urbana\u2014Champaign","place":["Urbana, USA"]},{"id":[{"id":"https:\/\/ror.org\/05p1j8758","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Pathobiology and Diagnostic Medicine, Kansas State University","place":["Manhattan, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ipshita","family":"Upadhyay","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/047426m28","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Pathobiology, University of Illinois at Urbana\u2014Champaign","place":["Urbana, USA"]},{"id":[{"id":"https:\/\/ror.org\/05p1j8758","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Pathobiology and Diagnostic Medicine, Kansas State University","place":["Manhattan, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyesuk","family":"Seo","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/047426m28","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Pathobiology, University of Illinois at Urbana\u2014Champaign","place":["Urbana, USA"]},{"id":[{"id":"https:\/\/ror.org\/05p1j8758","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Pathobiology and Diagnostic Medicine, Kansas State University","place":["Manhattan, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sai S. 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