#12-120

Complete

Date Full Report Received

02/18/2014

Date Abstract Report Received

02/18/2014

Investigation

Institution:
Primary Investigator:
 Virus neutralization (VN) activity following vaccination or infection with porcine reproductive respiratory syndrome virus (PRRSV) is generally considered to be weak and primarily directed against the virus used for infection; i.e. homologous neutralizing (nAb). However, under some circumstances, virus infection/vaccination can elicit cross-protection against a different isolate, in which case the VN response is called heterologous. For this project we took advantage of the samples generated through the PRRS Host Genetics Consortium (PHGC) to identify pigs that possess unique VN properties. Performing over 1,200 virus neutralization assays on samples from pigs experimentally infected with PRRSV, we identified a small percentage of pigs that produced antibodies capable of neutralizing a wide range of genetically diverse PRRSV isolates, which we termed broadly neutralizing antibody (bnAb). We identified several epitopes in PRRSV structural proteins, M, GP5 and GP3 that are associated with the bnAb response. The Identification of antigens that induce a broadly neutralizing response creates the opportunity to develop the next generation of vaccines. Another aspect of vaccine immunity is host genetics. The second objective of the project was to identify pig genomic markers related to the antibody response to PRRSV. The goal is to identify genes that enhance immunity to PRRS vaccines as a means to breed a “vaccine ready” pig. The VN response of pigs was only weakly heritable. One challenge was the wide variation between VN assays, partly a consequence of the subjective nature of the test. As a result, we developed a new VN assay for experimental samples that incorporates fluorescent viruses and eliminates the subjective nature of the VN assay. We also measured non-neutralizing total antibody (tAb), using a Luminex. Analysis of over 1,400 PHGC samples from the PHGC. A genome wide association study linked tAb with two regions on chromosome 7, both of which map to genes that are directly involved in the host immune response. Overall, the results of this study have direct applications for the next generation of PRRSV vaccines. The identification of regions within PRRSV linked with nAb groups creates the opportunity to design vaccines tailored to induce the production of bnAb. Moreover, identification of genomic markers linked with tAb creates the opportunity to produce pig lines which produce a more favorable immune response to the virus.
Raymond R.R. Rowland,browland@vet.k-state.edu, 785-532-4631.