Abstract
Since 2019, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has posed a global health threat. Its high transmissibility and cross-species infectivity have disrupted public health systems and worldwide economies, with companion and agricultural animals, like cats and minks, showing high susceptibility. This study evaluated rAd5-S6P, a recombinant vaccine using an adenovirus type 5 vector expressing a modified SARS-CoV-2 spike protein, in murine, feline, and mink models. Results demonstrated that rAd5-S6P elicited a robust humoral immune response when administered via intramuscular, intranasal, and oral routes, which conferred complete protection in mice. In feline and mink models, immunization with rAd-S6P resulted in significantly reduced viral shedding after high-dose SARS-CoV-2 challenge, and no infectious virus was detected in any of the examined organs of minks. Collectively, rAd5-S6P exhibited protective efficacy across species, supporting its translational potential as a veterinary vaccine. These findings provide critical evidence for animal vaccination strategies to control SARS-CoV-2 circulation and reduce zoonotic transmission risks.