#14-214

Complete

Date Full Report Received

05/02/2016

Date Abstract Report Received

05/02/2016

Investigation

Institution:
Primary Investigator:
Co-Investigators: Eric A. Nelson, Fernando Osorio, Jane Christopher-Hennings, Hiep Vu

Since its emergence in domestic pigs in the late 1980’s, porcine reproductive and respiratory syndrome virus (PRRSV) has caused significant economic losses to swine producers worldwide. A recent study in the US has estimated annual losses of approximately 650 million dollars to the pork industry due to PRRSV infection. Control of PRRSV and consequent reduction of the burden posed by the disease to swine producers and the pork industry have been major challenges to veterinarians and scientists working with swine health research both in industry- and academic-settings.

Control of PRRSV has been hindered by the lack of an effective vaccine capable of 1) eliciting early effector humoral- and cell-mediated immune responses against PRRSV; and of 2) providing cross-protection against heterologous PRRSV isolates. Currently available PRRSV vaccines (modified-live virus [MLV] and killed virus [KV]) elicit delayed neutralizing antibody- (NA) and cell-mediated responses and provide only partial protection to heterologous PRRSV strains. The complex interactions of PRRSV with the host immune system coupled with the high genetic and antigenic diversity of the virus are the main factors contributing to the failure of current vaccines in controlling PRRSV. Therefore identification of regions of the PRRSV genome (antigens/proteins and/or epitopes), capable of eliciting protection would facilitate the design and development of the next generation of PRRSV vaccines.

Recent studies have identified multiple antigenic epitopes on PRRSV genome. These studies create opportunities for rational design of improved subunit PRRSV vaccines. In the present study we sought to evaluate the role of antigenic PRRSV epitopes on protection against PRRSV infection and disease. The overall goal of this study is to evaluate the immunogenicity of antigenic epitopes of PRRSV and to evaluate their ability to induce protection against PRRSV.

The objectives of the study are:
Objective 1: To develop and express polyepitope proteins of PRRSV encoding B and T cell epitopes.
Objective 2: To assess the immunogenicity of PRRSV polyepitope proteins in pigs and their ability to induce protective immunity after PRRSV challenge.

PRRSV B and T-cell multi-epitope proteins were generated and expressed in a virus vector or as recombinant proteins in bacteria. These two approaches were used to deliver the PRRSV antigens in pigs and their ability to provide protection was evaluated after PRRSV challenge.
Antibody responses were detected against PRRSV epitopes by ELISA. Responses against individual epitopes were evaluated in serum samples collected at different time points post-immunization. Antibodies were detected against 11 of the 16 PRRSV antigens included in our recombinant protein construct. Notably, following challenge infection, no differences were observed in the clinical parameters evaluated between immunized and non-immunized animals, suggesting that the levels of antibodies generated might not be enough for protection or that these epitopes do not play an important role for PRRSV protection. No detectable cell mediated responses were observed in immunized animals, suggesting a low overall immunogenicity of the T-cell antigenic determinants used in our study. Taken together the results from our indicate an overall low immunogenicity of individual PRRSV epitopes. Identification of PRRSV strains capable of eliciting broad cross-protection and use if these strains to produce broadly protective vaccines might still be the best approach to develop the next generation of improved PRRSV vaccines.

Contact information: Diego G. Diel
Box 2175 North Campus Dr
South Dakota State University
Brookings, SD 57007
E-mail: diego.diel@sdstate.edu
Phone: 605-688-6645