Development of Adenovirus-vectored Prototype Vaccines for African Swine Fever Virus and Bovine Viral Diarrhea Virus

Abstract

The objective of this work was to develop adenovirus-vectored prototype vaccines against two pathogens, African Swine Fever Virus (ASFV) and Bovine Viral Diarrhea Virus (BVDV), which cause disease in two major livestock species, swine and cattle respectively.

The African Swine Fever Virus is a transboundary animal pathogen that causes a lethal hemorrhagic fever in domestic pigs. Attempts to develop a vaccine for ASFV have failed thus far. This manuscript describes the use of recombinant adenovirus to deliver two unique formulations of ASFV antigens in swine (in two separate in-vivo studies) and the subsequent evaluation of the antigen-specific antibody and cellular responses induced. The robust antigen-specific immune responses observed in both studies are promising and their protective potential will be evaluated in future efficacy studies

The Bovine Viral Diarrhea Virus is a globally prevalent pathogen that can cause severe diarrhea, respiratory disease, abortions and sometimes death in calves. Killed and modified live vaccines (MLV) for BVDV have been in use since the 1960s but are not effective due to lack of cross-protection and retention of immunosuppressive characteristics. This thesis also describes the use of the recombinant adenovirus vector to deliver a cocktail of multiple mosaic BVDV antigens in calves followed by the evaluation of protection conferred upon challenge. The prototype vaccine was more immunogenic and cross-protective (based on neutralizing antibodies) than a commercial MLV BVDV vaccine. Regarding protective efficacy, all calves immunized with prototype vaccine cleared the virus within a week post-challenge, whereas one calf that received the MLV vaccine still remained viremic. Future efficacy studies with diverse BVDV strains are required to validate the cross-protective potential of this prototype vaccine.