Abstract
Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) is the causative agent of one of the most important porcine diseases with a high impact on animal health, welfare, and production economy. PRRSV exhibits a multitude of immunoevasive strategies that, in combination with a very high mutation rate, has hampered the development of safe and broadly protective vaccines. Aiming at a vaccine inducing an effective cytotoxic T cell response, a bioinformatics approach was taken to identify conserved PRRSV-derived peptides predicted to react broadly with common swine leukocyte antigen (SLA) class I alleles. Briefly, all possible 9- and 10-mer peptides were generated from 104 complete PRRSV type 2 genomes of confirmed high quality, and peptides with high binding affinity to five common SLAs were identified combining the NetMHCpan and positional scanning combinatorial peptide libraries binding predictions. Predicted binders were prioritized according to genomic conservation and SLA coverage using the PopCover algorithm. From this, 53 peptides were acquired for further analysis. Binding affinity and stability of a subset of 101 peptide-SLA combinations were validated in vitro for 4 of the 5 SLAs. Eventually, 23% of the predicted peptide-SLA combinations showed to form complexes with a dissociation half-life ≥30 min. Additionally, combining the two prediction methods proved to be more robust across alleles than either method used alone in terms of predicted-to-observed correlations. In summary, our approach represents a finely tuned epitope prediction pipeline providing a rationally selected ensemble of peptides for future in vivo experiments with pigs expressing the included SLAs.
Highlights
Porcine Reproductive and Respiratory Syndrome (PRRS) is one of the most important porcine diseases in all swineproducing countries and has a high impact on animal health, Immunogenetics (2017) 69:689–702 welfare, and production economy (Nieuwenhuis et al 2012; Holtkamp et al 2013)
While these two factors are central in the definition of a peptide ensemble, weight coefficients could be adjusted in relation to the individual strains, peptides, and swine leukocyte antigen (SLA) alleles, in order to fine-tune the definition of the ensemble
Peptides derived from ORF1b will be much less abundant compared to peptides derived from ORF1a, and should be reflected by their weight coefficients
Summary
Porcine Reproductive and Respiratory Syndrome (PRRS) is one of the most important porcine diseases in all swineproducing countries and has a high impact on animal health, Immunogenetics (2017) 69:689–702 welfare, and production economy (Nieuwenhuis et al 2012; Holtkamp et al 2013). PRRSV exists in two genotypes that were recently classified as distinct species: PRRSV-1 and PRRSV-2 They are both members of the Arteriviridae family in the only assigned genus, Arterivirus, together with 11 other species including lactate dehydrogenase elevating virus and equine arteritis virus, the latter being type species for the genus. Studies have shown that infectious PRRSV could be isolated from lymphoid tissue more than 150 days after infection even after several months of viral absence in the serum (Wills et al 1997; Allende et al 2000). Viral replication has been detected for as long as 250 days after infection (Wills et al 2003). Viremia typically peaks after 10–15 days post infection and in most cases the level of virus in serum is below the detection limit 4 weeks after infection, but the virus may persist in some pigs (Lopez and Osorio 2004). The infection is not persistent per se, it is often lifelong since the average lifetime of production pigs is 180 days
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