Characterization of Coxiella burnetii infection in cynomolgus macaques.

Abstract

Q fever, caused by Coxiella burnetii, leads to debilitating human infections that are often recalcitrant to antibiotics. The development of new medical countermeasures is critical, as the only available vaccine has significant limitations that prevent its widespread or rapid use. To address this, we characterized aerosol C. burnetii infection in 16 cynomolgus macaques (Macaca fascicularis), providing the first detailed pathological description of Q fever pneumonia in a nonhuman primate model. Following exposure, all animals developed clinical signs consistent with human Q fever, including sustained fever, respiratory distress, and weight loss. Clinical pathology revealed hematological changes and evidence of systemic inflammation, including elevated C-reactive protein. Although clinical signs resolved by day 28, significant pathology persisted, including granulomatous interstitial pneumonia, pleuritis, carditis, hepatitis, and nephritis. Infection was confirmed in tissues using immunohistochemistry and electron microscopy. The cynomolgus macaque model faithfully replicates key features of human Q fever, validating its utility for studying disease pathogenesis and serving as a pivotal model for evaluating next-generation vaccines and therapies.