PRRSV possesses multiple immunoevasive strategies, from suppression of the host cell antiviral machinery, to the deceptive induction of a non-neutralizing antibody response through decoy antigen presentation.
This, combined with a very high mutation rate, has hampered the development of safe and effective vaccines.
With the overall aim to design a vaccine that induces an effective CTL response against PRRSV, we have taken a bioinformatics approach to identify common PRRSV epitopes predicted to react broadly with predominant swine MHC (SLA) alleles. First, the genomic integrity and sequencing method was examined for 334 available complete PRRSV type 2 genomes leaving 104 strains of high quality. For each strain, a library of all possible 9- and 10-mer peptides was generated considering the known ribosomal frame shift sites and sites for post translational cleavage.
All peptides were in silico analyzed for binding affinity to either of five common SLA class I alleles. A quantitative rank score was generated for each peptide by combining two algorithms based on the NetMHCpan neural network and lab determined SLA binding affinity of each amino acid at any position in the peptide, respectively.
Peptides with a rank score above a predefined threshold were further analyzed by the PopCover algorithm, providing a final list of 54 epitopes prioritized according to maximum coverage of PRRSV strains and SLA alleles.
This bioinformatics approach provides a rational strategy for selecting peptides for a CTL-activating vaccine with broad coverage of both virus and swine diversity. The immunogenicity of the selected peptides is in the process of being verified in vivo.
|Publication status||Published - 2015|
|Event||Keystone Symposia on Molecular and Cellular Biology: Accelerating life science discovery - Keystone Resort, Keystone, United States|
Duration: 20 Jan 2015 → 25 Jan 2015
|Conference||Keystone Symposia on Molecular and Cellular Biology: Accelerating life science discovery|
|Period||20/01/2015 → 25/01/2015|
Simon Welner (Recipient), 20 Jan 2015
Prize: Prizes, scholarships, distinctions