Novel Transcriptional and Translational Biomarkers of Tularemia Vaccine Efficacy in a Mouse Inhalation Model: Proof of Concept.

subspecies ( is extremely virulent for humans when inhaled as a small particle aerosol (<5 µm). Inhalation of ≥20 viable bacteria is sufficient to initiate infection with a mortality rate ≥30%. Consequently, in the past, became a primary candidate for biological weapons development. To counter this threat, the USA developed a live vaccine strain (LVS), that showed efficacy in humans against inhalation of virulent . However, the breakthrough dose was fairly low, and protection waned with time. These weaknesses triggered extensive research for better vaccine candidates. Previously, we showed that deleting the gene from virulent strain, SCHU S4, resulted in a mutant that was significantly less virulent than LVS for mice, yet better protected them from aerosol challenge with wild-type SCHU S4. To date, comprehensive searches for correlates of protection for SCHU S4 Δ among molecules that are critical signatures of cell-mediated immunity, have yielded little reward. In this study we used transcriptomics analysis to expand the potential range of molecular correlates of protection induced by vaccination with SCHU S4 Δ beyond the usual candidates. The results provide proof-of-concept that unusual host responses to vaccination can potentially serve as novel efficacy biomarkers for new tularemia vaccines.