Innate Immune Defenses Induced by CpG Do Not Promote Vaccine-Induced Protection against Foot-and-Mouth Disease Virus in Pigs

Abstract

Emergency vaccination as part of the control strategies against foot-and-mouth disease virus (FMDV) has the potential to limit virus spread and reduce large-scale culling. To reduce the time between vaccination and the onset of immunity, immunostimulatory CpG was tested for its capacity to promote early protection against FMDV challenge in pigs. To this end, CpG 2142, an efficient inducer of alpha interferon, was injected intramuscularly. Increased transcription of Mx1, OAS, and IRF-7 was identified as a sensitive measurement of CpG-induced innate immunity, with increased levels detectable to at least 4 days after injection of CpG formulated with Emulsigen. Despite this, CpG combined with an FMD vaccine did not promote protection. Pigs vaccinated 2 days before challenge had disease development, which was at least as acute as that of unvaccinated controls. All pigs vaccinated 7 days before challenge were protected without a noticeable effect of CpG. In summary, our results demonstrate the caution required when translating findings from mouse models to natural hosts of FMDV.Foot-and-mouth disease (FMD) represents one of the most economically important diseases of cloven-hoofed livestock. Its causative agent, FMD virus (FMDV), belongs to the Picornaviridae family and is a member of the genus Aphthovirus, together with equine rhinitis A virus. Infection with FMDV occurs commonly via the respiratory tract following contact or inhalation of airborne virus, with the major site of primary replication being the mucosal epithelia of the nasopharynx.In Europe, the current control strategy of an FMD outbreak relies on a nonvaccination policy. In the case of an epidemic, the primary actions against the spread of the disease have been culling of the affected herds, including preemptive slaughtering in a control zone, together with strict control of animal movement. Such drastic measures resulted in the slaughter of 6.5 million animals during the European outbreak in 2001. As a consequence, a strong desire to reduce reliance on large-scale culling of animals to control future outbreaks of FMD has developed, and one of the control measures being considered is the application of emergency vaccination. However, due to the exceptional rapidity of virus spread during FMD outbreaks, one important element for improving current vaccines is the promotion of an early induction of protection.FMDV infection elicits a rapid humoral response, followed by clearance of the opsonized virus complexes by phagocytic cells (20). Protection against FMDV correlates with the induction of high levels of neutralizing antibodies in serum, already detectable after 3 to 4 days postinfection (8). However, trials using high-dose conventional vaccines based on inactivated FMDV in cattle (9), pigs (26), and sheep (6) have shown that animals can be protected as early as 4 days postvaccination, in the absence of significant levels of neutralizing antibodies in the serum. This indicates that mechanisms other than specific antibodies were involved. For the curren...

The effect of the TLR9 ligand CpG-oligodeoxynucleotide on the protective immune response to alcelaphine herpesvirus-1-mediated malignant catarrhal fever in cattle

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