An inactivated human adenovirus type 55 vaccine attenuates pulmonary pathology in a non-human primate challenge model

Human adenovirus type 55 (HAdV-55) is an emerging respiratory pathogen associated with severe pneumonia and acute respiratory disease, yet no licensed vaccine is currently available. Here, we evaluated the immunogenicity and protective efficacy of an inactivated HAdV-55 vaccine formulated with aluminum hydroxide (iHAdV-55 + AH) in cynomolgus macaques. Animals received a prime-boost intramuscular immunization, and HAdV-55-specific binding IgG and neutralizing antibody responses were monitored longitudinally for up to 52 weeks. Protective efficacy was assessed in two independent respiratory challenge studies using combined intranasal and intratracheal inoculation with either a high dose (1 × 10¹¹ plaque forming unit: PFU) or a low dose (1 × 10⁹ PFU) of HAdV-55. Vaccination induced HAdV-55-specific binding and neutralizing antibody responses that remained detectable throughout the 52-week study period. Following the high-dose challenge, vaccinated macaques showed reduced pulmonary lesion burden on chest computed tomography, lower relative lung weights, and attenuated histopathological changes compared with phosphate-buffered saline (PBS) controls. In the low-dose challenge model, where overall disease manifestations were milder, vaccinated animals consistently exhibited fewer radiologic abnormalities, reduced inflammatory cell infiltration, and decreased viral shedding in nasal swabs. No evidence of vaccine-enhanced respiratory disease was observed in either challenge setting. Together, these findings indicate that iHAdV-55 + AH is immunogenic and attenuates HAdV-55-induced pulmonary pathology in this non-human primate model, supporting further development of inactivated vaccine strategies against severe HAdV-55 infection.