Abstract
Porcine respiratory coronavirus (PRCV) infection in pigs provides a physiologically and immunologically relevant large-animal model for acute respiratory coronavirus disease and vaccine evaluation. We investigated a replication-defective adenovirus (Ad) vaccine platform that enables display of antigens on the Ad capsid surface using the DogTag/DogCatcher protein superglue system. Ad vectors encoding the PRCV135 Spike (S) and Nucleocapsid (N) proteins were evaluated with or without surface decoration with the PRCV135 Spike receptor-binding domain (RBD). Both Ad(SN) and RBD-decorated Ad(SN)-RBD135 vaccines were protective against PRCV135 challenge. RBD135 decoration significantly enhanced neutralizing antibody titers in serum and bronchoalveolar lavage. In contrast, aerosol immunization with Ad(N) induced robust T cell responses but no protection. A multivalent cocktail of RBD-decorated Ad vectors targeting PRCV, porcine hemagglutinating encephalomyelitis virus (PHEV), and porcine deltacoronavirus (PDCoV) elicited antibodies against all three pathogens. This study demonstrates the versatility and potency of antigen-decorated Ad vectors as a platform for next-generation coronavirus vaccines in a relevant large natural host model.