In Vivo Model of Pulmonary Inflammation Induced by HAdV-55 Infection in Cynomolgus Monkeys: A Preclinical Model for Vaccine and Therapeutic Development 9181

Abstract Description Human adenovirus type 55 (HAdV-55), a recombinant strain of HAdV-11 and HAdV-14, is a pathogen that causes respiratory infections, including acute. Developing an animal model that mimics human infection is essential for understanding the disease. In this study, we established a cynomolgus monkey model of HAdV-55 infection via intratracheal and nasal route. The virus infected monkeys exhibited clinical signs, including nasal discharge, cough, weight loss, increased respiratory, and heart rates. In addition, hAdV55 infection induced pneumonia characterized by peri-bronchial consolidation, ground opacity, granulomatous inflammation, and macrophage infiltration. Hematological analysis revealed phase-specific responses, with early increases in neutrophils and basophils, followed by delayed elevations in eosinophils and large unstained cells. Cytokine profiling showed rapid increases in IFN-γ, IFN-β, and IL-6, delayed elevation of IL-8, and a decline in IL-4. Adaptive immune responses were marked by hAdV55-specific antibody production at 7 days and neutralizing antibodies at 3 days post-infection. Cellular immune responses, measured by IFN-γ-producing cells, were not detected within 14 days. These findings demonstrate that hAdV55 infection in cynomolgus monkeys replicates key aspects of human disease, establishing a robust model for studying hAd55 pathogenesis and advancing vaccine and therapeutic development. Funding Sources Supported by a grant from the Health and Medical Technology Research and Development project from the Ministry of Health & Welfare, Republic of Korea (Grant No. RS-2023-00264541) Topic Categories Viral Immunology (VIR)