#17-184 IPPA


Date Full Report Received


Date Abstract Report Received



Primary Investigator:

Porcine epidemic diarrhea virus (PEDV) is the causative agent of porcine epidemic diarrhea (PED), an enteric disease affecting the global swine industries. In the U.S., PEDV was detected for the first time in 2013. The PEDVs associated with the initial outbreak in the U.S. in April 2013 are highly virulent and belong to the Emerging North American non-S INDEL clade; these PEDVs were also called “U.S. original PEDV strain” or “U.S. prototype PEDV strain”. A clinically milder PEDV variant strain identified in January 2014 in the U.S. was called “S-INDEL PEDV strain”. Recently, new variants of PEDV with large deletions (194aa-204aa deletions) in the N-terminal domain of the spike protein have been identified in the U.S. swine samples and referred to as “S1 NTD-del variant”. However, these S1 NTD-del PEDV variant did not cause severe diarrhea in experimentally infected young pigs and its prevalence seems to be low. Diagnostics and research are mainly focused on U.S. prototype PEDV and S-INDEL PEDV strains.

Experimental infection studies have demonstrated that the U.S. S-INDEL PEDV isolates overall had lower pathogenicity than the U.S. prototype PEDV isolates in conventional neonatal piglets at 3-4 days of age or 5-6 days of age. However, pathogenicity and antibody responses of these two PEDV strains in older pigs have not been well characterized. This study aimed to compare pathogenicity and antibody responses of these two PEDV strains in three ages of pigs.

Thirty 3-week-old (“weaned”), thirty 8-week-old (“grower”), and thirty 23-week-old (“finisher”) pigs totaling 90 PEDV naïve pigs were included. Thirty pigs of each age were divided into 3 groups (10 pigs/group) and orogastrically inoculated with prototype PEDV (105 TCID50/pig), S-INDEL PEDV (105 TCID50/pig), or virus-negative medium. Half the pigs in each group were randomly selected for necropsy at 4 DPI and remaining pigs were necropsied at 28 DPI. Virus loads in rectal swabs, oral fluids, and various tissues collected at 4 DPI necropsy were determined by a quantitative PEDV N gene-based real-time RT-PCR. Tissues collected at 4 DPI necropsy were also subject to histopathological and immunohistochemistry examinations. Five pigs in each group that went through 28 DPI were compared for antibody responses. Serum neutralizing antibody was measured by a fluorescent focus neutralization assay using prototype PEDV as the indicator virus. Serum IgG and oral fluid IgA antibodies were measured by PEDV fluorescent microsphere immunoassay (FMIA) based on the N-terminal portion (S1) of the prototype PEDV spike protein.

In “weaned” pigs, prototype PEDV had longer duration of fecal shedding and significantly higher fecal and oral fluid virus loads than S-INDEL PEDV. In “grower” pigs, S-INDEL PEDV had longer fecal shedding than prototype PEDV; S-INDEL fecal virus load was significantly higher than prototype PEDV at 7 and 14 DPI but was opposite at 10 DPI. In “finisher” pigs, the onset of prototype PEDV fecal shedding was earlier and fecal virus load was higher than S-INDEL PEDV. For prototype PEDV, the onset of fecal virus shedding was earliest and shedding level was highest in “weaned”, followed by “grower” and “finisher” pigs. S-INDEL PEDV trended similarly when compared across age groups. The data suggest that pathogenicity of PEDV is pig age-dependent (more severe in younger pigs) and virus strain-dependent. Prototype PEDV appeared to be more pathogenic than S-INDEL PEDV in “weaned” and “finisher” pigs, but pathogenicity difference of two viruses was less distinct in “grower” pigs.

Neutralizing antibody, serum IgG and oral fluid IgA responses indicated that prototype PEDV induced greater antibody responses than S-INDEL PEDV in both “weaned” and “finisher” pigs, while the difference of antibody responses induced by two PEDV strains in “grower” pigs was not a clear cut and it depends on antibody assay. Prototype PEDV induced similar neutralizing antibody responses in three ages of pigs, stronger serum IgG responses in “weaned” pigs than in “grower” and “finisher” pigs, and stronger oral fluid IgA responses in “finisher” pigs than in “grower” and “weaned” pigs. Interestingly, S-INDEL PEDV appeared to consistently induce stronger antibody responses in “grower” pigs than in “weaned” and “finisher” pigs.

In summary, this study suggests that pathogenicity and antibody response of PEDV is both virus strain-dependent and pig age dependent. The data provide some guidance on selecting appropriate PEDV strain to induce antibody response in different age of pigs. It is noteworthy that different antibody assays may not always give the consistent results. For PEDV, mucosal immunity is critical for protection. However, at this point, it is unclear which antibody assay can better reflect mucosal and protective immunity although secretory IgA in small intestines is believed to be associated with mucosal and protective immunity. Nonetheless, it is not easy to routinely measure secretory IgA in small intestines. Work is in progress to assess the correlation of PEDV neutralizing antibody, serum IgG, and oral fluid IgA with secretory IgA in small intestines with the hope of finding an antibody assay that can be routinely conducted to reflect mucosal immunity.

For more information, please contact Dr. Jianqiang Zhang at Department of Veterinary Diagnostic and Production Animal Medicine, College of Veterinary Medicine, Iowa State University. E-mail: jqzhang@iastate.edu