{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T20:37:21Z","timestamp":1791405441934,"version":"4.3.3"},"reference-count":60,"publisher":"American Society for Microbiology","issue":"6","license":[{"start":{"date-parts":[[2014,6,1]],"date-time":"2014-06-01T00:00:00Z","timestamp":1401580800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Infect Immun"],"published-print":{"date-parts":[[2014,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Currently, there is no FDA-approved vaccine against\n            <jats:named-content content-type=\"genus-species\">Yersinia pestis<\/jats:named-content>\n            , the causative agent of bubonic and pneumonic plague. Since both humoral immunity and cell-mediated immunity are essential in providing the host with protection against plague, we developed a live-attenuated vaccine strain by deleting the Braun lipoprotein (\n            <jats:italic>lpp<\/jats:italic>\n            ) and plasminogen-activating protease (\n            <jats:italic>pla<\/jats:italic>\n            ) genes from\n            <jats:named-content content-type=\"genus-species\">Y. pestis<\/jats:named-content>\n            CO92. The \u0394\n            <jats:italic>lpp<\/jats:italic>\n            \u0394\n            <jats:italic>pla<\/jats:italic>\n            double isogenic mutant was highly attenuated in evoking both bubonic and pneumonic plague in a mouse model. Further, animals immunized with the mutant by either the intranasal or the subcutaneous route were significantly protected from developing subsequent pneumonic plague. In mice, the mutant poorly disseminated to peripheral organs and the production of proinflammatory cytokines concurrently decreased. Histopathologically, reduced damage to the lungs and livers of mice infected with the \u0394\n            <jats:italic>lpp<\/jats:italic>\n            \u0394\n            <jats:italic>pla<\/jats:italic>\n            double mutant compared to the level of damage in wild-type (WT) CO92-challenged animals was observed. The \u0394\n            <jats:italic>lpp<\/jats:italic>\n            \u0394\n            <jats:italic>pla<\/jats:italic>\n            mutant-immunized mice elicited a humoral immune response to the WT bacterium, as well as to CO92-specific antigens. Moreover, T cells from mutant-immunized animals exhibited significantly higher proliferative responses, when stimulated\n            <jats:italic>ex vivo<\/jats:italic>\n            with heat-killed WT CO92 antigens, than mice immunized with the same sublethal dose of WT CO92. Likewise, T cells from the mutant-immunized mice produced more gamma interferon (IFN-\u03b3) and interleukin-4. These animals had an increasing number of tumor necrosis factor alpha (TNF-\u03b1)-producing CD4\n            <jats:sup>+<\/jats:sup>\n            and CD8\n            <jats:sup>+<\/jats:sup>\n            T cells than WT CO92-infected mice. These data emphasize the role of TNF-\u03b1 and IFN-\u03b3 in protecting mice against pneumonic plague. Overall, our studies provide evidence that deletion of the\n            <jats:italic>lpp<\/jats:italic>\n            and\n            <jats:italic>pla<\/jats:italic>\n            genes acts synergistically in protecting animals against pneumonic plague, and we have demonstrated an immunological basis for this protection.\n          <\/jats:p>","DOI":"10.1128\/iai.01595-13","type":"journal-article","created":{"date-parts":[[2014,4,1]],"date-time":"2014-04-01T04:23:04Z","timestamp":1396326184000},"page":"2485-2503","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":25,"title":["Deletion of Braun Lipoprotein and Plasminogen-Activating Protease-Encoding Genes Attenuates Yersinia pestis in Mouse Models of Bubonic and Pneumonic Plague"],"prefix":"10.1128","volume":"82","author":[{"given":"Christina J.","family":"van Lier","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Sha","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle L.","family":"Kirtley","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony","family":"Cao","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bethany L.","family":"Tiner","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatiana E.","family":"Erova","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingzi","family":"Cong","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas, USA"},{"name":"Sealy Center for Vaccine Development, University of Texas Medical Branch, Galveston, Texas, USA"},{"name":"Center for Biodefense and Emerging Infectious Diseases, University of Texas Medical Branch, Galveston, Texas, USA"},{"name":"Institute of Human Infections and Immunity, University of Texas Medical Branch, Galveston, Texas, USA"},{"name":"Department of Pathology, University of Texas Medical Branch, Galveston, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena V.","family":"Kozlova","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vsevolod L.","family":"Popov","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Texas Medical Branch, Galveston, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wallace B.","family":"Baze","sequence":"additional","affiliation":[{"name":"Department of Veterinary Sciences, University of Texas M. 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Anderson Cancer Center, Bastrop, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashok K.","family":"Chopra","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas, USA"},{"name":"Sealy Center for Vaccine Development, University of Texas Medical Branch, Galveston, Texas, USA"},{"name":"Center for Biodefense and Emerging Infectious Diseases, University of Texas Medical Branch, Galveston, Texas, USA"},{"name":"Institute of Human Infections and Immunity, University of Texas Medical Branch, Galveston, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(07)60566-2"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.3121\/cmr.4.3.189"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1053\/j.spid.2006.07.002"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.10.1.35"},{"key":"e_1_3_2_6_2","volume-title":"Interregional meeting on prevention and control of plague, Antanarivo, Madagascar, 1 to 11 April","author":"World Health Organization","year":"2006","unstructured":"World Health Organization. 2006. Interregional meeting on prevention and control of plague, Antanarivo, Madagascar, 1 to 11 April. World Health Organization, Geneva, Switzerland. http:\/\/www.who.int\/csr\/resources\/publications\/WHO_HSE_EPR_2008_3w.pdf."},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(13)70323-2"},{"key":"e_1_3_2_8_2","volume-title":"Plague: questions and answers about plague","author":"World Health Organization Media Center","year":"2009","unstructured":"World Health Organization Media Center. 6 August 2009, posting date. Plague: questions and answers about plague. World Health Organization, Geneva, Switzerland. http:\/\/www.who.int\/ith\/diseases\/plague\/en\/."},{"key":"e_1_3_2_9_2","first-page":"18","volume-title":"Biological weapons proliferation: reasons for concern, courses of action","author":"Pearson GS","year":"1998","unstructured":"PearsonGSWoollettGRChevrierMITuckerJBSmithsonAE. 1998. 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