{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T19:37:39Z","timestamp":1793129859389,"version":"4.5.0"},"reference-count":37,"publisher":"American Society for Microbiology","issue":"9","license":[{"start":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T00:00:00Z","timestamp":1788825600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T00:00:00Z","timestamp":1788825600000},"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":[[2026,9,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      The high virulence and pathogenesis of\n                      <jats:italic toggle=\"yes\">Francisella tularensis<\/jats:italic>\n                      (\n                      <jats:italic toggle=\"yes\">Ft<\/jats:italic>\n                      ), responsible for tularemia, made it a target for bioweapon development during the \u201cCold War.\u201d This prompted investigation of vaccines, starting with an older vaccine candidate denoted\n                      <jats:italic toggle=\"yes\">Ft<\/jats:italic>\n                      live vaccine strain (LVS). LVS has limited efficacy against aerosol challenge with\n                      <jats:italic toggle=\"yes\">Ft<\/jats:italic>\n                      subsp. Tularensis (Type A), the most virulent subtype. However, no vaccines, including LVS, have been licensed in the U.S. Animal studies indicate that\n                      <jats:italic toggle=\"yes\">Ft<\/jats:italic>\n                      vaccines induce protective T-cell-mediated immune responses. In previous studies, analyses of leukocytes from vaccinated animals that were restimulated\n                      <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                      facilitated screening and selection of vaccines for more extensive\n                      <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                      evaluation. These studies demonstrated that a novel live attenuated vaccine strain derived from Type A\n                      <jats:italic toggle=\"yes\">Ft<\/jats:italic>\n                      , denoted\n                      <jats:italic toggle=\"yes\">\u0394clpB<\/jats:italic>\n                      , was protective against aerosol challenge in animal models. In this study, we focused on evaluating immune responses immediately after vaccination of Fischer 344 rats with LVS and\n                      <jats:italic toggle=\"yes\">\u0394clpB<\/jats:italic>\n                      using multiple analytical approaches. While humoral immune responses were comparable between the two vaccines, we identified multiple differences in immune responses by analyses of peripheral blood leukocytes by flow cytometry and by relative gene expression. In particular, vaccination with LVS or\n                      <jats:italic toggle=\"yes\">\u0394clpB<\/jats:italic>\n                      resulted in differential expression of multiple genes at selected time points. Gene expression, in turn, predicted activation or inhibition of multiple biological pathways. These results suggest that immune responses shortly after primary vaccination may discriminate vaccines with different degrees of\n                      <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                      protection that could potentially be used as correlates of protection and extrapolate efficacy from animals to people.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/iai.00208-26","type":"journal-article","created":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T13:46:46Z","timestamp":1786715206000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":0,"title":["Transcriptional analyses of peripheral blood lymphocytes obtained shortly after primary immunization discriminate vaccines against\n                    <i>Francisella tularensis<\/i>"],"prefix":"10.1128","volume":"94","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9663-7756","authenticated-orcid":true,"given":"Roberto","family":"De Pascalis","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02nr3fr97","id-type":"ROR","asserted-by":"publisher"}],"name":"Laboratory of Mucosal Pathogens and Cellular Immunology, Division of Bacterial, Parasitic and Allergenic Products, Center for Biologics Evaluation and Research, Food and Drug Administration","place":["Rockville, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott","family":"Espich","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02nr3fr97","id-type":"ROR","asserted-by":"publisher"}],"name":"Laboratory of Mucosal Pathogens and Cellular Immunology, Division of Bacterial, Parasitic and Allergenic Products, Center for Biologics Evaluation and Research, Food and Drug Administration","place":["Rockville, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hamda","family":"Khan","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02nr3fr97","id-type":"ROR","asserted-by":"publisher"}],"name":"Laboratory of Mucosal Pathogens and Cellular Immunology, Division of Bacterial, Parasitic and Allergenic Products, Center for Biologics Evaluation and Research, Food and Drug Administration","place":["Rockville, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mykia","family":"Toney","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02nr3fr97","id-type":"ROR","asserted-by":"publisher"}],"name":"Laboratory of Mucosal Pathogens and Cellular Immunology, Division of Bacterial, Parasitic and Allergenic Products, Center for Biologics Evaluation and Research, Food and Drug Administration","place":["Rockville, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chou","family":"Chao-Kai","sequence":"additional","affiliation":[{"name":"Office of Director, Science Staff, Center for Biologics Evaluation and Research, Food and Drug Administration","place":["Rockville, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wu","family":"Wells","sequence":"additional","affiliation":[{"name":"Office of Director, Science Staff, Center for Biologics Evaluation and Research, Food and Drug Administration","place":["Rockville, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8779-8657","authenticated-orcid":true,"given":"Karen L.","family":"Elkins","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02nr3fr97","id-type":"ROR","asserted-by":"publisher"}],"name":"Laboratory of Mucosal Pathogens and Cellular Immunology, Division of Bacterial, Parasitic and Allergenic Products, Center for Biologics Evaluation and Research, Food and Drug Administration","place":["Rockville, USA"]},{"name":"Office of Director, Science Staff, Center for Biologics Evaluation and Research, Food and Drug Administration","place":["Rockville, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_5_2_2","doi-asserted-by":"publisher","DOI":"10.3201\/eid1207.051504"},{"key":"e_1_3_5_3_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.285.21.2763"},{"key":"e_1_3_5_4_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.87.4.415"},{"key":"e_1_3_5_5_2","doi-asserted-by":"publisher","DOI":"10.1001\/archinte.1961.03620050068007"},{"key":"e_1_3_5_6_2","doi-asserted-by":"publisher","DOI":"10.1001\/archinte.1961.03620050055006"},{"key":"e_1_3_5_7_2","doi-asserted-by":"publisher","DOI":"10.1128\/br.26.3.354-373.1962"},{"key":"e_1_3_5_8_2","first-page":"282","article-title":"Recent studies on live tularemia vaccine","volume":"36","author":"Eigelsbach HT","year":"1967","unstructured":"Eigelsbach HT, Hornick RB, Tulis JJ. 1967. 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