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A vaccine that is safer and more effective than the currently available unlicensed<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">F. tularensis<\/jats:named-content>live vaccine strain (LVS) is needed to protect against intentional release of aerosolized<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">F. tularensis<\/jats:named-content>, the most dangerous type of exposure. In this study, we employed a heterologous prime-boost vaccination strategy comprising intradermally administered LVS \u0394<jats:italic>capB<\/jats:italic>(highly attenuated<jats:italic>capB<\/jats:italic>-deficient LVS mutant) as the primer vaccine and rLm\/iglC (recombinant attenuated<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Listeria monocytogenes<\/jats:named-content>expressing the<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">F. tularensis<\/jats:named-content>immunoprotective antigen IglC) as the booster vaccine. Boosting LVS \u0394<jats:italic>capB<\/jats:italic>-primed mice with rLm\/iglC significantly enhanced T cell immunity; their splenic T cells secreted significantly more gamma interferon (IFN-\u03b3) and had significantly more cytokine (IFN-\u03b3 and\/or tumor necrosis factor [TNF] and\/or interleukin-2 [IL-2])-producing CD4<jats:sup>+<\/jats:sup>and CD8<jats:sup>+<\/jats:sup>T cells upon<jats:italic>in vitro<\/jats:italic>IglC stimulation. Importantly, mice primed with LVS \u0394<jats:italic>capB<\/jats:italic>or rLVS \u0394<jats:italic>capB<\/jats:italic>\/IglC, boosted with rLm\/iglC, and subsequently challenged with 10 50% lethal doses (LD<jats:sub>50<\/jats:sub>) of aerosolized highly virulent<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">F. tularensis<\/jats:named-content>Schu S4 had a significantly higher survival rate and mean survival time than mice immunized with only LVS \u0394<jats:italic>capB<\/jats:italic>(<jats:italic>P<\/jats:italic>&lt; 0.0001); moreover, compared with mice immunized once with LVS, primed-boosted mice had a higher survival rate (75% versus 62.5%) and mean survival time during the first 21 days postchallenge (19 and 20 days for mice boosted after being primed with LVS \u0394<jats:italic>capB<\/jats:italic>and rLVS \u0394<jats:italic>capB<\/jats:italic>\/IglC, respectively, versus 17 days for mice immunized with LVS) and maintained their weight significantly better (<jats:italic>P<\/jats:italic>&lt; 0.01). Thus, the LVS \u0394<jats:italic>capB<\/jats:italic>-rLm\/iglC prime-boost vaccination strategy holds substantial promise for a vaccine that is safer and at least as potent as LVS.<\/jats:p>","DOI":"10.1128\/iai.01013-12","type":"journal-article","created":{"date-parts":[[2013,2,26]],"date-time":"2013-02-26T04:15:24Z","timestamp":1361852124000},"page":"1550-1561","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":28,"title":["A Heterologous Prime-Boost Vaccination Strategy Comprising the Francisella tularensis Live Vaccine Strain<i>capB<\/i>Mutant and Recombinant Attenuated Listeria monocytogenes Expressing F. tularensis IglC Induces Potent Protective Immunity in Mice against Virulent F. tularensis Aerosol Challenge"],"prefix":"10.1128","volume":"81","author":[{"given":"Qingmei","family":"Jia","sequence":"first","affiliation":[{"name":"Division of Infectious Diseases, Department of Medicine, Center for Health Sciences, School of Medicine, University of California\u2014Los Angeles, Los Angeles, California, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard","family":"Bowen","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Colorado State University, Fort Collins, Colorado, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jacob","family":"Sahakian","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Department of Medicine, Center for Health Sciences, School of Medicine, University of California\u2014Los Angeles, Los Angeles, California, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Barbara Jane","family":"Dillon","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Department of Medicine, Center for Health Sciences, School of Medicine, University of California\u2014Los Angeles, Los Angeles, California, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marcus A.","family":"Horwitz","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Department of Medicine, Center for Health Sciences, School of Medicine, University of California\u2014Los Angeles, Los Angeles, California, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1196\/annals.1409.009"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1099\/ijs.0.022830-0"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/97.2.162"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.5.1.77-82.1972"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1001\/archinte.1961.03620050055006"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1001\/archinte.1961.03620050068007"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1196\/annals.1409.013"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa011374"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.187.11.3903-3908.2005"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.2006.05061.x"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.73.12.8345-8352.2005"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00196-09"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1128\/br.25.3.262-267.1961"},{"key":"e_1_3_3_15_2","doi-asserted-by":"crossref","first-page":"415","DOI":"10.4049\/jimmunol.87.4.415","article-title":"Prophylactic effectiveness of live and killed tularemia vaccines. 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