Immunity & infection
Coxiella burnetii is a gram negative, obligate intracellular bacterium that is the causative agent of Q fever, a debilitating disease that can evolve into a fatal chronic infection resulting in endocarditis or neurological manifestations up to 20 years following the initial infection. C. burnetii is designated as a Category B pathogen due to its potential as a robust bioterrorism agent. Despite these facts, the only vaccine that currently exists is licensed in Australia and significant concerns about safety and efficacy necessitate the development of a safer and more effective vaccine. Our research group has developed a novel vaccine adjuvant system by conjugating three Toll-like receptor (TLR) agonists together to form a tri-agonist adjuvant. Using this tri-agonist adjuvant we have developed and tested novel C. burnetii vaccine candidates in vitro and in vivo for safety, immune stimulating activity and protection in a live C. burnetii infection challenge study. We have previously shown that our tri-agonist adjuvants elicit a more balanced Th1 and Th2 immune response and successfully increased antibody scope and diversity compared to non-adjuvanted vaccine candidates, suggesting downstream changes in immune signaling and adaptive immune activation. Here we show that our Q fever vaccination model, formulated with our tri-agonist adjuvant construct, elicits productive and effective adaptive immune responses in both a naïve vaccination model and a live C. burnetti infection. Our studies suggest that our novel C. burnetti vaccine could be an effective and safer alternative to the only vaccine currently available.
United States Army Medical Research Institute for Infectious Diseases