{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T20:15:25Z","timestamp":1792181725817,"version":"4.4.0"},"reference-count":47,"publisher":"American Society for Microbiology","issue":"10","license":[{"start":{"date-parts":[[2010,10,1]],"date-time":"2010-10-01T00:00:00Z","timestamp":1285891200000},"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":[[2010,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            <jats:italic>Francisella tularensis<\/jats:italic>\n            , the causative agent of tularemia, is in the top category (category A) of potential agents of bioterrorism. The\n            <jats:italic>F. tularensis<\/jats:italic>\n            live vaccine strain (LVS) is the only vaccine currently available to protect against tularemia; however, this unlicensed vaccine is relatively toxic and provides incomplete protection against aerosolized\n            <jats:italic>F. tularensis<\/jats:italic>\n            , the most dangerous mode of transmission. Hence, a safer and more potent vaccine is needed. As a first step toward addressing this need, we have constructed and characterized an attenuated version of LVS, LVS \u0394\n            <jats:italic>capB<\/jats:italic>\n            , both as a safer vaccine and as a vector for the expression of recombinant\n            <jats:italic>F. tularensis<\/jats:italic>\n            proteins. LVS \u0394\n            <jats:italic>capB<\/jats:italic>\n            , with a targeted deletion in a putative capsule synthesis gene (\n            <jats:italic>capB<\/jats:italic>\n            ), is antibiotic resistance marker free. LVS \u0394\n            <jats:italic>capB<\/jats:italic>\n            retains the immunoprotective O antigen, is serum resistant, and is outgrown by parental LVS in human macrophage-like THP-1 cells in a competition assay. LVS \u0394\n            <jats:italic>capB<\/jats:italic>\n            is significantly attenuated in mice; the 50% lethal dose (LD\n            <jats:sub>50<\/jats:sub>\n            ) intranasally (i.n.) is &gt;10,000-fold that of LVS. Providing CapB in\n            <jats:italic>trans<\/jats:italic>\n            to LVS \u0394\n            <jats:italic>capB<\/jats:italic>\n            partially restores its virulence in mice. Mice immunized with LVS \u0394\n            <jats:italic>capB<\/jats:italic>\n            i.n. or intradermally (i.d.) developed humoral and cellular immune responses comparable to those of mice immunized with LVS, and when challenged 4 or 8 weeks later with a lethal dose of LVS i.n., they were 100% protected from illness and death and had significantly lower levels (3 to 5 logs) of LVS in the lung, liver, and spleen than sham-immunized mice. Most importantly, mice immunized with LVS \u0394\n            <jats:italic>capB<\/jats:italic>\n            i.n. or i.d. and then challenged 6 weeks later by aerosol with 10\u00d7 the LD\n            <jats:sub>50<\/jats:sub>\n            of the highly virulent type A\n            <jats:italic>F. tularensis<\/jats:italic>\n            strain SchuS4 were significantly protected (100% survival after i.n. immunization). These results show that LVS \u0394\n            <jats:italic>capB<\/jats:italic>\n            is significantly safer than LVS and yet provides potent protective immunity against virulent\n            <jats:italic>F. tularensis<\/jats:italic>\n            SchuS4 challenge.\n          <\/jats:p>","DOI":"10.1128\/iai.00192-10","type":"journal-article","created":{"date-parts":[[2010,7,20]],"date-time":"2010-07-20T01:53:39Z","timestamp":1279590819000},"page":"4341-4355","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":53,"title":["A\n            <i>Francisella tularensis<\/i>\n            Live Vaccine Strain (LVS) Mutant with a Deletion in\n            <i>capB<\/i>\n            , Encoding a Putative Capsular Biosynthesis Protein, Is Significantly More Attenuated than LVS yet Induces Potent Protective Immunity in Mice against\n            <i>F. tularensis<\/i>\n            Challenge"],"prefix":"10.1128","volume":"78","author":[{"given":"Qingmei","family":"Jia","sequence":"first","affiliation":[{"name":"Division of Infectious Diseases, Department of Medicine, 37-121 Center for Health Sciences, School of Medicine, University of California\u2014Los Angeles, 10833 Le Conte Avenue, Los Angeles, California 90095-1688"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bai-Yu","family":"Lee","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Department of Medicine, 37-121 Center for Health Sciences, School of Medicine, University of California\u2014Los Angeles, 10833 Le Conte Avenue, Los Angeles, California 90095-1688"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Bowen","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Colorado State University, Fort Collins, Colorado 80523"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara Jane","family":"Dillon","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Department of Medicine, 37-121 Center for Health Sciences, School of Medicine, University of California\u2014Los Angeles, 10833 Le Conte Avenue, Los Angeles, California 90095-1688"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan M.","family":"Som","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Department of Medicine, 37-121 Center for Health Sciences, School of Medicine, University of California\u2014Los Angeles, 10833 Le Conte Avenue, Los Angeles, California 90095-1688"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcus A.","family":"Horwitz","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Department of Medicine, 37-121 Center for Health Sciences, School of Medicine, University of California\u2014Los Angeles, 10833 Le Conte Avenue, Los Angeles, California 90095-1688"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","unstructured":"Alibek K. 1999. 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