Research project Francisella tularensis is a highly virulent bacterial human pathogen that causes tularemia, a common disease in certain parts of the world, in particular in Sweden and Finland. A live vaccine strain (LVS) was empirically derived in the 1950’s, but it confers incomplete protection. We hypothesize that a more efficacious vaccine will be possible to develop and the overall goal of the ongoing work is to develop models that can identify the efficacy of new vaccines.
Francisella tularensis is a highly virulent bacterial human pathogen that causes tularemia, a common disease in certain parts of the world, in particular in Sweden and Finland. A live vaccine strain (LVS) was empirically derived in the 1950’s, but it confers incomplete protection. We hypothesize that a more efficacious vaccine will be possible to develop and the overall goal of the ongoing work is to develop models that can identify the efficacy of new vaccines.
In support, we have generated a candidate vaccine, ∆clpB, which is highly attenuated and demonstrates better protective efficacy than does LVS. One important aim of the ongoing work is to identify correlates of protection to validate this new vaccine candidate.
The first goal of the proposed studies is to use a combination of immunological and molecular tools to map the exact specificities of the F. tularensis-specific human memory immune T cells. Thus, we will characterize the phenotypes of the memory cells by means of secreted cytokines, expression of intracellular cytokines, and surface markers. Essential for this, we have a unique, large panel of longitudinal cell samples collected from individuals following vaccination or infection with F. tularensis.
We will validate the signatures identified in the human system by using mouse, rat, and macaque models to demonstrate their contribution to protection. Further, we aim to identify the immunological parameters that gives ∆clpB superior protective efficacy compared to LVS.
