Coxiella burnetii immunobiology, host-pathogen modeling, and countermeasure development

National Institute Of Allergy And Infectious Diseases

Investigators

Linked publications & trials

Abstract

Coxiella burnetii is a bacterium that can cause a severe flu-like illness in humans known as Q fever. This zoonotic infection is typically acquired via aerosol transmission of contaminated byproducts of infected ruminants. The pronounced infectivity and environmental stability of C. burnetii highlights its utility as a potential bioweapon. The public health impact of Q fever was illustrated by a recent dairy goat-associated outbreak in the Netherlands resulting in nearly 4000 human cases. This outbreak demonstrated the human health burden and staggering economic losses that can result from this infectious disease. Despite Coxiella burnetii's near worldwide presence and potential for harm, both as a zoonosis and a potential bioweapon, much still remains unknown regarding host-pathogen interactions. Additionally, a safe and effective vaccine licensed for use in the United States remains elusive due to a potential post-vaccination hypersensitivity (PVH) response. We are particularly interested in understanding virulence determinants, immune correlates of vaccine-mediated protective immunity, and mechanisms of PVH. Thus, we have developed guinea pig models of infection, vaccination-challenge, and post-vaccination hypersensitivity. Genetically modified C. burnetii strains have been created and tested as viable vaccine candidates and have been used to identify C. burnetii virulence factors and bacterial structures involved in additional host-pathogen interactions. Additionally, we recently introduced a murine model of PVH which revealed sex dimorphic responses. Together, we have utilized these systems to identify novel virulence factors of C. burnetii, screen vaccine candidates, and work towards developing a non-reactive vaccine. We are developing and validating complementary animal models of host-pathogen interactions, further expanding the guinea pig model, and performing detailed immunologic analysis of these interactions. Our program will continue to develop and utilize animal models of host-pathogen interactions paired with bacteriologic techniques to reveal important bacterial and host components of immune responses. Ultimately, this work will contribute to the development of an improved Q fever vaccine and therapeutics.