1a.Objectives (from AD-416)
The objective of this agreement is to investigate the role of dendritic cells response to Foot-and-Mouth Disease Virus (FMDV) infection and in response to vaccination against FMDV in swine and cattle. Development of an alternative platform for vaccination will be done at the Institute for Animal Health (IAH) that will endeavor to stabilize the virus capsid in the vaccine construct thereby rapidly inducing protective of antibody and cell mediated (T cell) immune responses. When these stabilized empty capsids become available, these new vaccines will be added to the analysis of new recombinant vaccines ongoing at USDA, PIADC and IAH.

1b.Approach (from AD-416)
The role of dendritic cells in the immune response to FMDV will be studied utilizing knowledge of dendritic cell biology in cattle and swine. Published data indicates that the innate responses of dendritic cells induced by vaccination contribute to inhibition of viral infection when animals are challenged at 7 days or less. Collaborating scientists from IAH have expertise in the isolation and evaluation of dendritic cells of cattle. ARS, PIADC has developed unique methods for isolating and analyzing dendritic cells of swine. Collaborative efforts will expand the studies into reactivity of dendritic cells following vaccination and progressing to the analysis of dendritic cell function in vivo.

Development of an alternative platform for vaccination is currently being developed at IAH. Analysis of the immune response to a number of different viruses suggests stable capsids are highly effective at driving antibody and cell mediated immune responses. IAH is currently seeking to develop immunological correlates of protection against FMDV, following vaccination with this new stabilized capsid vaccine. ARS, PIADC currently has empty capsid vaccine vectored by human Adeno5 virus under development. Though very promising as a vaccine vector, data indicate capsid stability may be limiting vaccine performance. These technologies will be merged, generating new vaccines that will be tested for efficacy.

3.Progress Report
This report documents research conducted under a non-funded cooperative agreement between ARS and the Institute for Animal Health (IAH), Pirbright, UK. Additional details of this research can be found in the report for the in-house associated project, 1940-32000-048-00D, "Development of Novel Strategies to Control Foot-and-Mouth Disease", NP 103, Animal Health. This project is related to objective 2, "Determine the mechanisms of early immune enhancement against Foot-and-Mouth Disease." The objective of this cooperative research project is to investigate the role of dendritic cells (DCs) in the response to Foot-and-Mouth Disease infection in swine and cattle. An additional objective is to apply technologies developed at IAH to stabilize the vaccine composed of nonviable virus (empty capsids). The respective laboratories have coordinated the ongoing studies in each into the role of dendritic cells in early, innate response to FMDV infection. IAH has extensive experience in isolation and analysis of bovine DCs and ARS, PIADC has extensive experience in porcine DCs. Together, we have provided critical input for reefing experiments and subsequent presentation of data for publication. In FY08, we will address the second objective; the human, replication defective adenovirus vector delivering recombinant FMDV antigens will be transferred from ARS, PIADC to IAH. In addition, the technology to propagate the virus will be transferred. Work has now been initiated in both laboratories to assess the innate response to the adenovirus vector and the immune parameters of the adeno vectored vaccine compared to the present, killed virus vaccine. Visits by ARS scientists to Pirbright, UK and the principal investigator from Pirbright to PIADC provided the opportunity to plan and initiate research objectives. This project was monitored through email and telephone exchange. Initial materials transfer was completed in May 07.