Epitope-based vaccination against pneumonic tularemia

The HLA class II DNA construct was mixed with in vivo-jetPEI. To promote mucosal immunity, HLA-DRB1- transgenic mice were inoculated intratracheally (i.t.) three times at 2-week intervals (i.e., on days 0, 14 and 28) with 25 µg DNA/50 µl saline. On days 42 and 56, the mice were boosted i.t. with 25µg/50 µl aliquots of the same class-II-restricted peptides encoded by the construct.

Francisella tularensis, the etiological agent of tularemia, is one of the most infectious bacterial pathogens known. No vaccine is currently approved for public use. Previously, we identified epitopes recognized specifically by T cells obtained from individuals following infection with F. tularensis. Here, we report that a subunit vaccine constructed based upon these epitopes elicited protective immunity in "humanized" HLA class II (DRB1*0401) transgenic mice. Vaccinated mice challenged intratracheally with a lethal dose of F. tularensis (Live Vaccine Strain) exhibited a rapid increase in pro-inflammatory cytokine production and diminished number of organisms in the lungs, and a concurrent increased rate of survival. These results demonstrate the efficacy of an epitope-based tularemia vaccine and suggest that such an approach might be widely applicable to the development of vaccines specific for intracellular bacterial pathogens.