Delivery of a foot-and-mouth disease virus empty capsid subunit antigen with nonstructural protein 2B improves protection of swine.

To develop a more efficacious human adenovirus (Ad5)-vectored foot-and-mouth disease virus (FMDV) subunit vaccine (Ad5-A24) we have included coding regions for FMDV nonstructural proteins 2B and 2C. These proteins are involved in membrane re-arrangements resulting in the proliferation of cytoplasmic vesicles which serve as the sites of virus replication. Cells infected with a vector containing full-length 2B (Ad5-CI-A24-2B) had a significant increase in the number of cytoplasmic vesicles as compared to cells infected with the original vector or a vector containing full-length 2BC. Swine inoculated with Ad5-CI-A24-2B developed an enhanced FMDV-specific neutralizing antibody response as compared to animals inoculated with the original vector and showed no clinical signs of disease after challenge. In a second experiment animals vaccinated with Ad5-CI-A24-2B were not fully protected but had a more rapid and robust humoral response and two out of three pigs had delayed and less severe disease than animals in the other vaccinated groups. These results suggest that incorporation of the complete coding region of 2B into the vaccine enhances its potency and protective efficacy.