Submitted to: Clinical and Vaccine Immunology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 6/18/2009
Publication Date: 8/1/2009
Citation: Alves, M.P., Guzylack-Piriou, L., Juillard, V., Audonnet, J.C., Doel, T., Dawson, H.D., Golde, W.T., Gerber, H., Peduto, N., Mccullough, K.C., Summerfield, A. 2009. Innate Immune Defenses Induced by CpG do not Promote Vaccine-Induced Protection Against Foot-and-Mouth Disease in Pigs. Clinical and Vaccine Immunology. 16(8):1151-1157. Interpretive Summary: We tested a promising additive termed an “adjuvant” to the commercially available vaccine for Foot-and-Mouth Disease Virus (FMDV). This formulation showed excellent activity in mouse studies for many vaccines including FMDV. In collaboration with the manufacturer, the new formulation was produced and tested in pigs, a natural host of FMDV. Data from these studies show that the vaccine performed very well but that the new additive had no effect on clinical outcome in vaccinated animals challenged with the virus. These studies highlight that biologicals, successfully tested in mouse “models”, often show no effect in the species of interest and caution should be very high when extrapolating results from mouse experiments.
Technical Abstract: Emergency vaccination as part of the control strategies against Foot-and-Mouth Disease (FMD) epidemics has the potential not only to limit the spread of the virus but also to reduce large-scale culling of affected herds. With the aim to reduce the time between vaccination and the onset of immunity, immunostimulatory CpG oligodeoxynucleotides (CpG ODNs) were tested for their capacity to provide early protection against FMD virus (FMDV) challenge in pigs. The transcription level of the genes encoding for Mx1, OAS and IRF-7 were identified as sensitive measurements of CpG-induced activation of innate antiviral defence, and were used to optimize CpG formulation. Elevated mRNA levels for these genes were detectable 8 h to at least 4 days after injection when CpG was formulated with Emulsigen. Despite this, vaccination of pigs with a combination of conventional FMD vaccine and CpG formulated in Emulsigen two days before challenge infection did not induce any protection. Applied at 7 days before challenge CpG did not influence the protective value of the vaccine. While our results demonstrate the potency of conventional FMD vaccines in severe heterologous challenge infection of pigs, the study also shows that caution is required when translating findings from mouse models to a natural host of FMDV.