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Pasteurella multocida can infect a multitude of wild and domesticated animals, with infections in cattle resulting in hemorrhagic septicemia (HS) or contributing to bovine respiratory disease (BRD) complex. Current cattle vaccines against P . multocida consist of inactivated bacteria, which only offer limited and serogroup specific protection. Here, we describe a newly identified surface lipoprotein, PmSLP, that is present in nearly all annotated P . multocida strains isolated from cattle. Bovine associated variants span three of the four identified phylogenetic clusters, with PmSLP-1 and PmSLP-2 being restricted to BRD associated isolates and PmSLP-3 being restricted to isolates associated with HS. Recombinantly expressed, soluble PmSLP-1 (BRD-PmSLP) and PmSLP-3 (HS-PmSLP) vaccines were both able to provide full protection in a mouse sepsis model against the matched P . multocida strain, however no cross-protection and minimal serum IgG cross-reactivity was identified. Full protection against both challenge strains was achieved with a bivalent vaccine containing both BRD-PmSLP and HS-PmSLP, with serum IgG from immunized mice being highly reactive to both variants. Year-long stability studies with lyophilized antigen stored under various temperatures show no appreciable difference in biophysical properties or loss of efficacy in the mouse challenge model. PmSLP-1 and PmSLP-3 vaccines were each evaluated for immunogenicity in two independent cattle trials involving animals of different age ranges and breeds. In all four trials, vaccination with PmSLP resulted in an increase in antigen specific serum IgG over baseline. In a blinded cattle challenge study with a recently isolated HS strain, the matched HS-PmSLP vaccine showed strong efficacy (75–87.5% survival compared to 0% in the control group). Together, these data suggest that cattle vaccines composed of PmSLP antigens can be a practical and effective solution for preventing HS and BRD related P . multocida infections.

Fowl cholera is one of the most serious and economically important infectious diseases of poultry caused by Pasteurella multocida . Formalin-inactivated vaccine, administered intramuscularly, is widely used in Ethiopia with a low success rate. Gamma irradiation is an effective approach to inactivate pathogens for vaccine development. In a previous study, we reported the feasibility of developing gamma-irradiated vaccines that induced both systemic and mucosal antibody responses with complete protection against homologous lethal challenge. In the present study, we aimed to broaden our understanding of the immunogenicity of the gamma-irradiated vaccines by including peripheral blood mononuclear cells (PBMC) response analysis. A total of 156 eight-week-old fowl cholera-specific antibody negative Bovans Brown chickens were utilized in this experiment. The performances of gamma-irradiated P. multocida vaccines formulated with different adjuvants, Montanide Gel 01 PR (G-1), Carbigen® (G-2), Emulsigen-D®+aluminum hydroxide gel (G-3), and Emulsigen-p® (G-4) were evaluated in comparison with the formalin-inactivated vaccine (G-5) and unvaccinated control (G-6). Chickens received two doses of the vaccines at days 0 and 21. Sera, tracheal, and crop lavage were collected at days 0, 21, 35, and 56 to assess IgG and IgA levels using indirect and sandwich ELISA, respectively. PBMC proliferation was compared between vaccinated and unvaccinated controls. In addition, vaccination-induced expression of cytokine genes was analyzed in PBMC using qPCR. Chickens were challenged with 2.5x107 CFU/ml of P. multocida biotype A intramuscularly one day after day-56 sampling. Significant serum IgG titers were detected three weeks after primary vaccination in G1, G3, and G5. IgG titer substantially increased in all vaccinated groups two weeks post-booster dose. IgA response was induced by gamma-irradiated vaccines but not formalin-inactivated vaccines. Only PBMC from vaccinated chickens proliferated in response to re-stimulation with P. multocida antigen, indicating vaccine-specific priming. Interestingly, gamma-irradiated vaccines resulted in a higher fold change in mRNA transcripts of IFN-γ (>1000-fold change) IL-6 (>500-fold change), and IL-12p40 (>200-fold change), which are hallmarks of a Th1 dominant response, which is essential to combat intracellular infection. Lastly, the candidate vaccines demonstrated various levels of protection, with Emulsigen-D® containing vaccine rendering complete protection against homologous lethal challenge. In conclusion, gamma-irradiated vaccines can induce broad immune responses, humoral and cellular, and protect against severe outcome of fowl cholera. Therefore, this study has contributed to growing knowledge on the immunogenicity and efficacy of gamma-irradiated vaccines and has shown the potential of such a vaccine platform for field application in extensive as well as intensive farm settings.