Overview of the Q fever vaccine development: current status and future prospects.

Coxiella burnetii, the causative agent of Q fever, is responsible for a globally significant zoonotic disease, characterized by flu-like symptoms. The primary reservoirs of C. burnetii are ruminant livestock, particularly goats, sheep, and cattle, which shed the bacterium through birth products, such as the placenta, amniotic fluid, and other secretions. Human infections typically occur via the inhalation of contaminated aerosols during direct or indirect contact with infected animals or their birthing materials. Consequently, individuals living in or working near livestock environments are at elevated risk, making Q fever both a location- and occupation-related disease. Owing to its remarkable environmental resilience and extremely low infectious dose, C. burnetii is classified as a Category B bioterrorism agent by the U.S. Centers for Disease Control and Prevention (CDC). These characteristics significantly complicate efforts to eradicate the bacterium and position vaccination as a key strategy for preventing human transmission. Although whole-cell vaccines (WCVs) are currently licensed for use in Australia, their widespread implementation has been hindered by their strong reactogenic responses in individuals with prior exposure to C. burnetii. This review provides an overview of past and current efforts to develop non-reactogenic C. burnetii vaccines and discusses possible approaches to enhance the efficiency and safety of these vaccines.