Activities of Murine Peripheral Blood Lymphocytes Provide Immune Correlates That Predict Francisella tularensis Vaccine Efficacy
We previously identified potential correlates of vaccine-induced protection againstFrancisella tularensisusing 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 withF. tularensisLive Vaccine Strain (LVS) and related attenuated strains, we combined the control ofin vitroFrancisellareplication within macrophages with gene expression analyses. Thein vitrofunctions of PBLs, particularly the control of intramacrophage LVS replication, reflected the hierarchy ofin vivoprotection 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, withoutex vivorestimulation, was different among vaccine groups, suggesting a potential tool to monitor efficacious vaccine-induced immune responses againstF. tularensis. Our studies demonstrate that murine PBLs can be used productively to identify potential correlates of protection againstF. tularensisand to expand and refine a comprehensive set of protective correlates.