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Establishment of a Cynomolgus Macaque Model for Human Adenovirus Type 55-Induced Respiratory Disease
Sang Hwan Seo1, Jung-Ah Choi1, Dae-Im Jung1
1Science Unit, International Vaccine Institute, Seoul, Republic of Korea.
Background:
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.
Methods:
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.
Results:
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.
Conclusions:
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.
Insights
A new cynomolgus macaque model effectively replicates human adenovirus type 55 (HAdV-55) respiratory disease. This breakthrough aids in studying HAdV-55 pathogenesis and evaluating new treatments.
Area of Science:
- * Virology and Immunology
- * Respiratory Pathogen Research
- * Nonhuman Primate Models
Background:
- * Human adenovirus type 55 (HAdV-55) is an emerging pathogen causing severe pneumonia outbreaks.
- * Limited nonhuman primate models hinder HAdV-55 research and therapeutic development.
Purpose of the Study:
- * To establish and characterize a cynomolgus macaque model for HAdV-55 infection.
- * To investigate the clinical, pathological, and immunological responses to HAdV-55 in macaques.
Main Methods:
- * Cynomolgus macaques were infected intranasally and intratracheally with HAdV-55 after a control period.
- * Clinical signs, blood work, cytokine levels, imaging, histopathology, and immune profiles were monitored.
Main Results:
- * Infected macaques developed respiratory symptoms, lung consolidation, and granulomatous inflammation.
- * Phase-specific hematological and cytokine responses were observed, including early IFN-γ, IFN-β, IL-6, and later IL-8 elevation.
- * Virus-specific and neutralizing antibodies developed, but T-cell responses were delayed.
Conclusions:
- * The cynomolgus macaque model accurately mimics human HAdV-55 respiratory disease.
- * This model serves as a valuable platform for studying HAdV-55 pathogenesis.
- * The model will facilitate preclinical evaluation of HAdV-55 vaccines and therapeutics.
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