| dc.description.abstract | Q fever is a zoonotic disease caused by the obligate intracellular bacterium, Coxiella burnetii. C. burnetii is highly infectious, transmitted via aerosols, is resistant to many disinfectants, and persists in the environment for long periods. The currently available vaccine licensed for use in humans is Q-VAX, a whole cell, formalin-inactivated vaccine. Although highly protective, the use of this vaccine is heavily restricted due to the high rate of local and systemic reactions in persons with prior exposure to C. burnetii. Despite decades of work understanding the mechanisms of protective efficacy of C. burnetii vaccines, little is known about the pathogenesis of their reactogenicity.
We began our work by testing novel subunit vaccines against C. burnetii which lacked the phase I lipopolysaccharide, an antigen that was previously proposed as a potential cause for reactogenicity. Our work showed that while these subunits vaccines provided significant protection from pulmonary infection, many of the formulations still produces local reactogenic responses. These results indicated that the mechanisms of reactogenicity with C. burnetii vaccines is more complex and required further investigation.
To better understand the pathogenesis of reactogenicity to the current whole cell vaccine, we developed a sensitized mouse model of reactogenicity. Our work on this model showed that reactogenicity to the whole cell vaccine is mediated by memory CD4 T cells and enhanced by immune serum. Additionally, these reactions are partially mediated by the production of IFNγ, indicating that C. burnetii whole cell vaccine reactogenicity is a Th1-mediated hypersensitivity reaction. Lastly, we showed that the whole cell vaccine causes local persistence of antigen at the injection site for at least six months which is likely contributing to the chronicity of local hypersensitivity reactions.
Overall, our work reveals some of the mechanisms of reactogenicity caused by the C. burnetii whole cell vaccine. Understanding the mechanisms behind vaccine reactogenicity provides information essential for the development safe and effective novel vaccines. | |
