Location: Virus and Prion Research
Project Number: 5030-32000-118-04-I
Project Type: Interagency Reimbursable Agreement
Start Date: Aug 8, 2014
End Date: Jul 30, 2018
1) Develop porcine epidemic diarrhea virus (PEDV) challenge models for pigs and sows. 2) Determine the presence and duration of cross-protective PEDV immunity in sows. 3) Determine the effect and duration of passively acquired PEDV immunity in pigs 4) Generate tissues, fecal material, and sera from PEDV/porcine delta coronavirus (PDCoV) studies for use by the National Veterinary Services Laboratories, USDA-APHIS. 5) Conduct basic research for the development of effective vaccines.
Extend existing research done by others (universities, biologics companies) and investigate gaps in understanding the ecology, pathogenesis, protective immunity, and vaccinology of novel swine enteric coronaviruses. ARS, with university and corporate partners, will conduct a series of experiments. A. Mechanisms of porcine delta coronavirus (PDCoV) pathogenesis, transmission, and protective immunity. The major focus is porcine epidemic diarrhea virus (PEDV), PDCoV, and other emerging swine enteric coronaviruses. PDCoV was recently isolated for the first time by the USDA-APHIS-NVSL. How PDCoV interacts with swine is unknown. Experiments using pigs of different ages will be conducted to characterize the pathogenesis, transmissibility, and onset of immunity for PDCoV. B. PEDV challenge models to test experimental vaccines. Currently, biologics companies are working on producing PEDV vaccines through traditional strategies involving attenuation and genetic engineering. Non-traditional PEDV vaccine technologies or vaccination routes need to be investigated. The goal is to enhance mucosal immunity that develops in a sow with the anticipation this will improve colostrum, and may produce a lactogenic immunity. Experiments will be conducted to determine the most efficient animal challenge models to evaluate vaccines. C. Evaluate vaccine prototypes. Efficacy of PEDV vaccine prototypes will be tested in challenge model(s) determined in Approach B. D. Determine management of colostrum and lactogenic immunity. The onset and duration of protective PEDV/PDCoV immunity in the sow and the quality and quantity of PEDV/PDCoV immunity that is transferred to piglets via colostrum and milk will be studied. Knowledge gained from our basic research program on swine lactogenic immunity will provide new opportunities to improve the management of passive transfer of immunity to protect neonatal pigs. This basic research is paramount to inform the development of effective vaccines that induce lactogenic immunity. E. Discover vaccine(s) for neonatal pigs that override maternal antibody interference. Examine experimental vaccine platforms, adjuvants and routes of inoculation that can be used to deliver immunogens to sows and piglets in the hope of inducing protective mucosal immunity. ARS will work jointly with vaccine companies that need support, but our initial research will utilize replication defective adenovirus vectors that we know work well in pigs with regards to inducing mucosal immunity against influenza virus when administered via mucosal surface routes. The replication defective adenovirus platform has an additional advantage in that it has been shown to work in the face of maternal immunity and it does not shed. F. Genetic virulence factors of PEDV. Current vaccine strategies focus on inducing an immune response against coronavirus spike proteins. This approach may not induce effective mucosal immunity and is susceptible to viral genetic variations and viral mechanisms of immune evasion. The goal is to identify determinants of virulence to design vaccines that will induce broad and effective protective immunity in sows and neonatal pigs.