Structure analysis of capsid protein of Porcine circovirus type 2 from pigs with systemic disease

Abstract

Economic losses with high mortality rate associated with Porcine circovirus type 2 (PCV2) is reported worldwide. PCV2 commercial vaccine was introduced in 2006 in U.S. and in 2008 in Brazil. Although PCV2 vaccines have been widely used, cases of PCV2 systemic disease have been reported in the last years. Eleven nursery or fattening pigs suffering from PCV2 systemic disease were selected from eight PCV2-vaccinated farms with historical records of PCV2 systemic disease in Southern Brazil. PCV2 genomes were amplified and sequenced from lymph node samples of selected pigs. The comparison among the ORF2 amino acid sequences of PCV2 isolates revealed three amino acid substitutions in the positions F57I, N178S and A190T, respectively. Using molecular modeling, a structural model for the capsid protein of PCV2 was built. Afterwards, the mutated residues positions were identified in the model. The structural analysis of the mutated residues showed that the external residue 190 is close to an important predicted region for antibodies recognition. Therefore, changes in the viral protein conformation might lead to an inefficient antibody binding and this could be a relevant mechanism underlying the recent vaccine failures observed in swine farms in Brazil.

One Dose of a Novel Vaccine Containing Two Genotypes of Porcine Circovirus (PCV2a and PCV2b) and Mycoplasma hyopneumoniae Conferred a Duration of Immunity of 23 Weeks

“…While PCV2a vaccines have been demonstrated to generate some cross-protection from clinical PCV2, associated disease PCV2 viruses continue to evolve and instances of vaccine failures due to diverse PCV2 field virus challenge have been documented [ 30 ]. PCV2 vaccines generally do not provide sterilizing immunity [ 30 , 31 ] and historic single genotype PCV2 vaccines may not induce broad enough cross-protection to cover evolving field viruses [ 32 ]. In fact, traditional single genotype PCV2 vaccine use has contributed to the selection of emergent viruses [ 33 ].…”

“…In fact, traditional single genotype PCV2 vaccine use has contributed to the selection of emergent viruses [ 33 ]. Emergent field viruses are especially different from vaccine strains in capsid epitopic regions [ 30 , 31 ]. Since the capsid is the immunodominant protein, shifts away from vaccine capsid epitopes may be contributing the vaccine failures.…”

The Monoclonal Antibody Recognized the Open Reading Frame Protein in Porcine Circovirus Type 2-Infected Peripheral Blood Mononuclear Cells

“…In contrast to the ORF3 protein, the detection of the capsid protein could be the variable result in PCV2-infected PBMCs via different antibodies, due to different PCV2 strains [49,74], conformational epitopes [75], or linear epitopes [49,76]. Previous studies indicated that antibody binding residues were often on the exterior of the capsid of PCV2 [48,49,70,74,77,78]. Although an epitope might be on the surface of the single capsid unit, it could bury in the VLP and be inaccessible to the antibody [79,80].…”

A bivalent porcine circovirus type 2 (PCV2), PCV2a-PCV2b, vaccine offers biologically superior protection compared to monovalent PCV2 vaccines

“…Genotypes a, b, and d are clinically relevant and most often associated with clinical PCV2-SD [ 3 , 10 ]. New virus genotypes including recombinants are continually being sequenced with changes focused primarily on the capsid (ORF2) genetic sequence [ 11 , 12 ].…”

“…Even minor changes in the capsid amino acid sequence can alter the configuration of conformational epitopes and thereby affect PCV2 pathogenicity and immune differentiation including binding of neutralizing antibodies [ 13 , 14 ]. A growing dissimilarity in epitopes shared among evolving field strains and constant vaccine strains may be contributing to decreasing efficacy of PCV2a vaccines [ 3 , 12 , 15 – 17 ]. The hypotheses that minor variations in epitopic regions can lead to differences in immune recognition [ 11 , 15 – 17 ] and escape from the vaccine-induced immune response [ 11 , 18 ] have been raised previously.…”