Establishment of a Cynomolgus Macaque Model for Human Adenovirus Type 55-Induced Respiratory Disease.

Abstract

Human adenovirus type 55 (HAdV-55) is an emerging respiratory pathogen associated with severe pneumonia outbreaks, particularly in military populations and community settings. The lack of a suitable nonhuman primate model has limited the study of viral pathogenesis and the evaluation of vaccines and therapeutics. Cynomolgus macaques were first administered phosphate-buffered saline intranasally and intratracheally as a negative control and allowed to recover for 20 days. The same animals were subsequently infected intranasally and intratracheally with HAdV-55. Clinical signs, hematologic parameters, cytokine responses, imaging, histopathology, and immunologic profiles were monitored over time. Infected macaques exhibited respiratory symptoms including nasal discharge, cough, weight loss, and increased respiratory and heart rates. Lung imaging revealed peri-bronchial consolidation and ground-glass opacities. Histopathology showed granulomatous inflammation and macrophage infiltration, resembling human disease. Hematological analysis demonstrated early neutrophilia and basophilia, followed by eosinophilia and increased numbers of large unstained cells. Cytokine profiling showed early induction of IFN-γ, IFN-β, and IL-6, with delayed IL-8 elevation and IL-4 suppression. This study establishes a cynomolgus macaque model that recapitulates key clinical and immunological features of HAdV-55-induced respiratory and provides a platform for the preclinical evaluation of vaccines and therapeutics.