Immunogenicity of an Orf Virus Vector-Based Vaccine Delivery Platform in Sheep

Background/Objective: Virus-based vaccine vectors have been widely utilised in commercial vaccines predominantly for virus infections. They also offer promise for bacterial diseases, for which many vaccines are sub-optimal or ineffective. It is well-established for chlamydial infections including ovine enzootic abortion that the major outer membrane protein (MOMP) antigen is protective. Immune responses strongly associated with controlling Chlamydiae include cellular interferon-gamma (IFN-γ) production. Methods: A study was conducted to compare the ability of a modified Orf virus vector directly with a modified sheep maedi visna virus vector to deliver the C. abortus antigen ompA and stimulate vaccine-induced responses in sheep. The Orf virus-based vaccine (mORFV-ompA) was found to be more effective in stimulating MOMP-specific antibody and cellular antigen-driven IFN-γ in immunised sheep. This mORFV-ompA vaccine was assessed in a follow-up immunogenicity investigation in sheep where the cellular and humoral immune responses elicited following immunisation with the live or inactivated vaccine were determined. Sheep were immunised intramuscularly with a live mORFV-ompA (n=10) or an inactivated mORFV-ompA (n=10). An additional group of 10 sheep served as unvaccinated controls. Results: Serological anti-MOMP antibodies and cellular recall responses of peripheral blood mononuclear cells to the native C. abortus antigen were assessed. Immunisation with either the live or inactivated mORFV-ompA induced anti-MOMP immunoglobulin-G. Antigen-specific cellular responses, characterised by the secretion of IFN-γ and interleukin (IL)-17A, with negligible IL-10 and no IL-4 were detected in lymphocyte stimulation assays from both mORFV groups. No antibody responses to the mORFV platform were detected following immunisations. Conclusions: Both live and inactivated vaccines have the potential to be a platform technology for deployment in sheep. This addresses a notable gap for veterinary vaccine development where the induction of both humoral responses and cellular responses are required without using an adjuvant. The successful use of the MOMP candidate antigen suggests potential utility for bacterial disease deployment.