{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T06:38:01Z","timestamp":1791095881142,"version":"4.1.0"},"reference-count":44,"publisher":"American Society for Microbiology","issue":"3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clin. Vaccine Immunol."],"published-print":{"date-parts":[[2014,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Studies were undertaken to manufacture a multivalent\n                    <jats:named-content content-type=\"genus-species\">Shigella<\/jats:named-content>\n                    inactivated whole-cell vaccine that is safe, effective, and inexpensive. By using several formalin concentrations, temperatures, and incubation periods, an optimized set of inactivation conditions was established for\n                    <jats:named-content content-type=\"genus-species\">Shigella flexneri<\/jats:named-content>\n                    2a,\n                    <jats:named-content content-type=\"genus-species\">S. sonnei<\/jats:named-content>\n                    , and\n                    <jats:named-content content-type=\"genus-species\">S. flexneri<\/jats:named-content>\n                    3a to produce inactivated whole cells expressing a full repertoire of Ipa proteins and lipopolysaccharide (LPS). The inactivation conditions selected were treatment with 0.2% formalin (\n                    <jats:named-content content-type=\"genus-species\">S. flexneri<\/jats:named-content>\n                    2a and 3a) or 0.6% formalin (\n                    <jats:named-content content-type=\"genus-species\">S. sonnei<\/jats:named-content>\n                    ) for 48 h at 25\u00b0C. Vaccine formulations prepared under different inactivation conditions, in different doses (10E5, 10E7, and 10E9 cells), and with or without the inclusion of double-mutant heat-labile toxin (dmLT) were evaluated in mice. Two intranasal immunizations with \u226510E7 inactivated whole cells resulted in high levels of anti-Invaplex and moderate levels of LPS-specific IgG and IgA in serum and in lung and intestinal wash samples. Addition of dmLT to the vaccine formulations did not significantly enhance humoral immunogenicity. Minimal humoral responses for IpaB, IpaC, or IpaD were detected after immunization with inactivated whole\n                    <jats:named-content content-type=\"genus-species\">Shigella<\/jats:named-content>\n                    cells regardless of the vaccine inactivation conditions. In guinea pigs, monovalent formulations of\n                    <jats:named-content content-type=\"genus-species\">S. flexneri<\/jats:named-content>\n                    2a of 3a or\n                    <jats:named-content content-type=\"genus-species\">S. sonnei<\/jats:named-content>\n                    consisting of 10E8, 10E9, or 10E10 cells were protective in a keratoconjunctivitis assay. A trivalent formulation provided protection against all three serotypes (\n                    <jats:named-content content-type=\"genus-species\">S. flexneri<\/jats:named-content>\n                    2a,\n                    <jats:italic>P<\/jats:italic>\n                    = 0.018;\n                    <jats:named-content content-type=\"genus-species\">S. flexneri<\/jats:named-content>\n                    3a,\n                    <jats:italic>P<\/jats:italic>\n                    = 0.04;\n                    <jats:named-content content-type=\"genus-species\">S. sonnei<\/jats:named-content>\n                    ,\n                    <jats:italic>P<\/jats:italic>\n                    &lt; 0.0001). The inactivated\n                    <jats:named-content content-type=\"genus-species\">Shigella<\/jats:named-content>\n                    whole-cell vaccine approach incorporates an uncomplicated manufacturing process that is compatible with multivalency and the future development of a broadly protective\n                    <jats:named-content content-type=\"genus-species\">Shigella<\/jats:named-content>\n                    vaccine.\n                  <\/jats:p>","DOI":"10.1128\/cvi.00683-13","type":"journal-article","created":{"date-parts":[[2014,1,9]],"date-time":"2014-01-09T01:05:54Z","timestamp":1389229554000},"page":"366-382","source":"Crossref","is-referenced-by-count":52,"title":["Development and Preclinical Evaluation of a Trivalent, Formalin-Inactivated Shigella Whole-Cell Vaccine"],"prefix":"10.1128","volume":"21","author":[{"given":"R. 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