{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T16:52:18Z","timestamp":1790009538359,"version":"4.0.1"},"update-to":[{"DOI":"10.1371\/journal.pntd.0009826","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2021,11,12]],"date-time":"2021-11-12T00:00:00Z","timestamp":1636675200000}}],"reference-count":50,"publisher":"Public Library of Science (PLoS)","issue":"10","license":[{"start":{"date-parts":[[2021,10,13]],"date-time":"2021-10-13T00:00:00Z","timestamp":1634083200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosntds.org"],"crossmark-restriction":false},"short-container-title":["PLoS Negl Trop Dis"],"abstract":"<jats:p>\n                    No vaccine to protect against an estimated 238,000 shigellosis deaths per year is widely available.\n                    <jats:italic>S<\/jats:italic>\n                    .\n                    <jats:italic>sonnei<\/jats:italic>\n                    is the most prevalent\n                    <jats:italic>Shigella<\/jats:italic>\n                    , and multiple serotypes of\n                    <jats:italic>S<\/jats:italic>\n                    .\n                    <jats:italic>flexneri<\/jats:italic>\n                    , which change regionally and globally, also cause significant disease. The leading\n                    <jats:italic>Shigella<\/jats:italic>\n                    vaccine strategies are based on the delivery of serotype specific O-antigens. A strategy to minimize the complexity of a broadly-protective\n                    <jats:italic>Shigella<\/jats:italic>\n                    vaccine is to combine components from\n                    <jats:italic>S<\/jats:italic>\n                    .\n                    <jats:italic>sonnei<\/jats:italic>\n                    with\n                    <jats:italic>S<\/jats:italic>\n                    .\n                    <jats:italic>flexneri<\/jats:italic>\n                    serotypes that induce antibodies with maximum cross-reactivity between different serotypes. We used the GMMA-technology to immunize animal models and generate antisera against 14\n                    <jats:italic>S<\/jats:italic>\n                    .\n                    <jats:italic>flexneri<\/jats:italic>\n                    subtypes from 8 different serotypes that were tested for binding to and bactericidal activity against a panel of 11\n                    <jats:italic>S<\/jats:italic>\n                    .\n                    <jats:italic>flexneri<\/jats:italic>\n                    bacteria lines. Some immunogens induced broadly cross-reactive antibodies that interacted with most of the\n                    <jats:italic>S<\/jats:italic>\n                    .\n                    <jats:italic>flexneri<\/jats:italic>\n                    in the panel, while others induced antibodies with narrower specificity. Most cross-reactivity could not be assigned to modifications of the O-antigen, by glucose, acetate or phosphoethanolamine, common to several of the\n                    <jats:italic>S<\/jats:italic>\n                    .\n                    <jats:italic>flexneri<\/jats:italic>\n                    serotypes. This allowed us to revisit the current dogma of cross-reactivity among\n                    <jats:italic>S<\/jats:italic>\n                    .\n                    <jats:italic>flexneri<\/jats:italic>\n                    serotypes suggesting that a broadly protective vaccine is feasible with limited number of appropriately selected components. Thus, we rationally designed a 4-component vaccine selecting GMMA from\n                    <jats:italic>S<\/jats:italic>\n                    .\n                    <jats:italic>sonnei<\/jats:italic>\n                    and\n                    <jats:italic>S<\/jats:italic>\n                    .\n                    <jats:italic>flexneri<\/jats:italic>\n                    1b, 2a and 3a. The resulting formulation was broadly cross-reactive in mice and rabbits, inducing antibodies that killed all\n                    <jats:italic>S<\/jats:italic>\n                    .\n                    <jats:italic>flexneri<\/jats:italic>\n                    serotypes tested. This study provides the framework for a broadly-protective\n                    <jats:italic>Shigella<\/jats:italic>\n                    vaccine which needs to be verified in human trials.\n                  <\/jats:p>","DOI":"10.1371\/journal.pntd.0009826","type":"journal-article","created":{"date-parts":[[2021,10,13]],"date-time":"2021-10-13T15:07:55Z","timestamp":1634137675000},"page":"e0009826","update-policy":"https:\/\/doi.org\/10.1371\/journal.pntd.corrections_policy","source":"Crossref","is-referenced-by-count":26,"title":["Rationalizing the design of a broad coverage Shigella vaccine based on evaluation of immunological cross-reactivity among S. flexneri serotypes"],"prefix":"10.1371","volume":"15","author":[{"given":"Francesco","family":"Citiulo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2122-9480","authenticated-orcid":true,"given":"Francesca","family":"Necchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Mancini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0170-1285","authenticated-orcid":true,"given":"Omar","family":"Rossi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9248-9362","authenticated-orcid":true,"given":"Maria Grazia","family":"Aruta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gianmarco","family":"Gasperini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renzo","family":"Alfini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simona","family":"Rondini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Micoli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rino","family":"Rappuoli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0665-4091","authenticated-orcid":true,"given":"Allan","family":"Saul","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7146-1283","authenticated-orcid":true,"given":"Laura B.","family":"Martin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2021,10,13]]},"reference":[{"key":"pntd.0009826.ref001","unstructured":"Institute for Health Metrics and Evaluation (IHME). 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