title: Activities of Murine Peripheral Blood Lymphocytes Provide Immune Correlates That Predict Francisella tularensis Vaccine Efficacy.
abstract: We previously identified potential correlates of vaccine-induced protection against Francisella tularensis using murine splenocytes and further demonstrated that the relative levels of gene expression varied significantly between tissues. In contrast to splenocytes, peripheral blood leukocytes (PBLs) represent a means to bridge vaccine efficacy in animal models to that in humans. Here we take advantage of this easily accessible source of immune cells to investigate cell-mediated immune responses against tularemia, whose sporadic incidence makes clinical trials of vaccines difficult. Using PBLs from mice vaccinated with F. tularensis Live Vaccine Strain (LVS) and related attenuated strains, we combined the control of in vitro Francisella replication within macrophages with gene expression analyses. The in vitro functions of PBLs, particularly the control of intramacrophage LVS replication, reflected the hierarchy of in vivo protection conferred by LVS-derived vaccines. Moreover, several genes previously identified by the evaluation of splenocytes were also found to be differentially expressed in immune PBLs. In addition, more extensive screening identified additional potential correlates of protection. Finally, expression of selected genes in mouse PBLs obtained shortly after vaccination, without ex vivo restimulation, was different among vaccine groups, suggesting a potential tool to monitor efficacious vaccine-induced immune responses against F. tularensis. Our studies demonstrate that murine PBLs can be used productively to identify potential correlates of protection against F. tularensis and to expand and refine a comprehensive set of protective correlates.
authors.affiliation: Laboratory of Mucosal Pathogens and Cellular Immunology, Division of Bacterial, Parasitic and Allergenic Products, Center for Biologics Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland, USA roberto.depascalis@fda.hhs.gov karen.elkins@fda.hhs.gov.
authors.forename: Roberto
authors.initials: R
authors.lastname: De Pascalis
authors.affiliation: Laboratory of Mucosal Pathogens and Cellular Immunology, Division of Bacterial, Parasitic and Allergenic Products, Center for Biologics Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland, USA.
authors.forename: Lara
authors.initials: L
authors.lastname: Mittereder
authors.affiliation: Laboratory of Mucosal Pathogens and Cellular Immunology, Division of Bacterial, Parasitic and Allergenic Products, Center for Biologics Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland, USA.
authors.forename: Nikki J
authors.initials: NJ
authors.lastname: Kennett
authors.affiliation: Laboratory of Mucosal Pathogens and Cellular Immunology, Division of Bacterial, Parasitic and Allergenic Products, Center for Biologics Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland, USA roberto.depascalis@fda.hhs.gov karen.elkins@fda.hhs.gov.
authors.forename: Karen L
authors.initials: KL
authors.lastname: Elkins
mesh_terms: D000818:Animals; D001428:Bacterial Vaccines / Q000276:immunology*; D018920:Coculture Techniques; D005604:Francisella tularensis / Q000276:immunology*; D005786:Gene Expression Regulation; D008214:Lymphocytes / Q000276:immunology / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D040081:Protein Array Analysis; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D013154:Spleen / Q000166:cytology; D014406:Tularemia / Q000517:prevention & control*
chemical_list: D001428:Bacterial Vaccines; D011506:Proteins
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