Bovine respiratory disease (BRD) is a complex condition influenced by a combination of environmental stressors, host immune responses, and multiple pathogens. It is most prevalent in young cattle that are housed in close quarters and was called shipping fever due to its association with animal movements. The economic consequences of BRD are significant worldwide, with one feedlot study showing more than one in six cattle being affected by BRD and over 2% mortality, with a reduction in net return of 50% in affected cattle. BRD is initiated in susceptible cattle by respiratory virus infections, with bovine herpesvirus 1 (BoHV-1), bovine respiratory syncytial virus (BRSV) and parainfluenza virus 3 (PI3) being among the most prevalent. Bacterial infections can also occur, in particular Mannheimia haemolytica and Pasteurella multocida which cause pneumonia, but are often a secondary infection leading to clinical disease.
At Moredun, we have developed vaccine vectors to deliver antigen payloads from the virus pathogens involved in BRD using four platforms. In this proposal, we have selected one protein from a bacterium, and one protein from a virus involved in BRD to compare our vaccine platforms. These will both be cloned into each of the vectors under study, specifically, replication defective human adenovirus 5 (Ad5), Maedi visna virus (MV), Alcelaphine herpesvirus 1 (AlHV-1), and Orf virus. All vaccine vectors we produce, expressing the targeted antigens, will be tested in vitro as a pre-screen before conducting animal trials. If, as expected, all express the protein payload in vitro, they will be tested in cattle. We will assay for serum antibody responses, mucosal antibody responses, and the comparative levels of CD4 T helper cell responses. There are no reports to date of direct comparison of different viral vaccine vectors delivering the same payload.
Results will provide data to determine if one or more of these vectors out-perform the others in the delivery of the selected antigens. Further, we will demonstrate whether these vectors induce stronger and more protracted immune responses than the same antigens given as recombinant proteins in adjuvant. If any of the vectored vaccines are superior performers, this will advance the development of more effective BRD vaccines. These vector systems allow for delivery of multiple proteins in a single payload, providing multivalent vaccines. They also allow rapid change of the payload if new, antigenically divergent strains of either bacteria or virus are identified. Additionally, these vectors do not require adjuvants for delivery, removing that expense and reducing injection reactions often seen with strong adjuvants.
Contact details:
Dr William Golde
Principal Research Scientist
Moredun Research Institute