Comparison of predicted T cell epitopes in porcine circovirus type 2 isolates from 2017 to 2021 and selected vaccines (EpiCC analysis) confirms the global relevance of a bivalent vaccine approach

Abstract

Porcine circovirus type 2 (PCV2) is a globally important pathogen of swine with a high capacity for genetic change, potentially including evolution of strains less susceptible to vaccine induced immunity. Starting with DNA sequences, in silico tools can be used to predict the T cell epitope content of the PCV2 capsid protein in vaccines and field strains, allowing calculation of Epitope Content Comparison (EpiCC) scores reflecting the number of T-cell epitopes held in common. Previous work has shown that a bivalent PCV2a and PCV2b vaccine gave greater T cell epitope coverage (higher EpiCC scores) than either PCV2a or PCV2b as a monovalent, with the more complete match potentially helping to preserve or enhance vaccine efficacy. This study extends the above, using refined methodology to compare the putative T-cell epitope content of 4 PCV2 vaccines (3 based on PCV2a, and one a PCV2a and PCV2b bivalent) to a larger and more contemporary global sample of PCV2 field strains. 746 PCV2, ORF2 nucleotide sequences from diagnostic submissions dating from 2017 to 2021 were included. These comprised PCV2a (129), PCV2b (109) and PCV2d (508), and originated from Asia (185), Europe (269), North America (235) and South America (57). Phylogenetic classification confirmed the predominance of PCV2d in all regions, but with continuing presence of PCV2a and PCV2b. An interesting regional divergence was noted for PCV2a, with all strains from Europe grouped within a single phylogenetic cluster (cluster 10) and all but one from North America being in a different phylogenetic cluster (cluster 6). EpiCC scores for the bivalent vaccine were significantly higher than for the monovalents for all genotypes in all regions, showing the global relevance of the bivalent approach. Calculation of the relative contributions of the PCV2a and PCV2b components showed that, while most T-cell epitopes were present in both, each also made substantial unique contributions. Of most practical relevance, given that most commercial vaccines are based on PCV2a, the addition of PCV2b increased T-cell epitope coverage by 33% and 21% for PCV2b and PCV2d respectively.