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

Microorganisms

Youlian Pan¹  Ziying Liu¹  Qing Yan Liu²  Felicity Stark²  Joseph Wayne Conlan²  Sonia Leclerc² 

[1] Digital Technologies Research Centre, National Research Council of Canada (NRC), Ottawa, ON K1A 0R6, Canada;Human Health Therapeutics Research Centre, National Research Council of Canada (NRC), Ottawa, ON K1A 0R6, Canada;

关键词: tularemia;    Francisella tularensis;    live attenuated vaccine;    transcriptomics;    correlates of protection;   

DOI  :  10.3390/microorganisms10010036

来源: DOAJ

【 摘 要 】

Francisella tularensis subspecies tularensis (Ftt) 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, Ftt 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 Ftt. 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 clpB gene from virulent Ftt 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 ΔclpB 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 ΔclpB 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.

【 授权许可】

Unknown