Vaccine-induced protective immunity against coxiella burnetii

Abstract

Coxiella burnetii is an obligate intracellular Gram-negative bacterial pathogen and the causative agent of human Q fever. This disease presents acutely as a flu-like illness, although it can escalate to a chronic and often fatal disease when left untreated. Considering no FDA-approved vaccine exists, the creation of a safe and effective vaccine remains an important public health goal. A formalin-inactivated C. burnetii Nine Mile strain phase I whole-cell vaccine generates protective immunity in a mouse model of experimental Q fever, although the mechanisms of protection remain unclear. Chapter 3 details my work establishing an early vaccine protection model and elucidating the cellular immune response which elicits early protection. The early time point at which PIV protects has implications for its use as a therapeutic vaccine. Furthermore, the innate-driven mechanisms by which it protects can be exploited for an improved Q fever vaccine. The importance of T cells in vaccine immunity against C. burnetii is well supported, however, multiple questions remain. It is unclear how CD4+ or CD8+ T cells contribute to vaccine protection, and the role of specific CD4+ T cell subsets is unknown. IFN-[theta] is critical for primary defense against C. burnetii, though its importance in vaccine immunity is undetermined. Chapter 4 describes my work aimed at filling these knowledge gaps. Vaccine development efforts have largely focused on the generation of antibodies as a correlate of protection. It has become clear that targeting T cells is more critical to vaccine protection and a better understanding of the mechanisms of cell-mediated immunity will inform future Q fever vaccine development.