Scientific Publications by FDA Staff

Infect Immun 2016 Mar 24;84(4):1054-61

Activities of murine peripheral blood lymphocytes provide immune correlates that predict Francisella vaccine efficacy.

De Pascalis R, Mittereder L, Kennett NJ, Elkins KL

We previously identified potential correlates of vaccine-induced protection against Francisella tularensis using murine splenocytes, and further demonstrated that 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 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 Live Vaccine Strain (LVS) and related attenuated strains, we combined control of in vitro Francisella replication within macrophages with gene expression analyses.The in vitro functions of PBLs, particularly control of LVS intramacrophage replication, reflected the hierarchy of in vivo protection by LVS-derived vaccines. Moreover, several genes, previously identified using splenocytes, were also differentially expressed in immune PBLs. In addition, more extensive screening identified additional potential correlates of protection. Finally, the expression of selected genes was different among vaccine groups in mouse PBLs obtained shortly after vaccination, without ex vivo re-stimulation, 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.