Mucosal immunization of calves with recombinant bovine adenovirus-3: induction of protective immunity to bovine herpesvirus-1

To determine the potential of replication-competent (ES-deleted) bovine ade novirus-3 (BAV-3) as a delivery system for vaccine antigens in calves, we e valuated the ability of recombinant BAV-3 expressing different forms of of bovine herpesvirus-l (BHV-1) glycoprotein go to protect against BHV-1 infec tion in calves that had pre-existing BAV-3 specific antibodies. Three- to f our-month-old calves, vaccinated intranasally with recombinant BAV-3 expres sing full-length go (BAV3.E3gD) or a truncated version of go (gDt) (BAV3.E3 gDt), or with E3-deleted BAV-3 (BAV3.E3d; control), were challenged with BH V-1 strain 108, Vaccination with BAV3.E3gD or BAV3.E3gDt induced gD-specifi c antibody responses in serum and nasal secretions, and primed calves for g o-specific lymphoproliferative responses. In addition, all calves developed complement-independent neutralizing antibodies against BHV-1. Protection a gainst viral challenge was observed in calves vaccinated with recombinant B AV3.E3gD or BAV3.E3gDt as shown by a significant reduction in body temperat ure and clinical disease, and a partial reduction in the amount and duratio n of virus excretion in nasal secretions. These results indicate that repli cation-competent BAV-3-based vectors can induce protective immune responses in calves (the natural host) that have pre-existing BAV-3-specific antibod ies.