Porcine circovirus type 2 (PCV2) is a pathogen of swine. Vaccines against PCV2 are available, although none are capable of differentiating infected from vaccinated animals (DIVA). Positive and negative DIVA markers were introduced in the vaccine constructs. Decoy epitopes were modified by site directed mutagenesis to avoid possible subversion of host immunity and achieve a rationalized vaccine design. Immunization of pigs with the modified vaccines, followed by challenge with a virulent field strain showed that the efficacy of the vaccine was comparable to a commercial vaccine. The average weight gain was significantly higher group vaccinated with experimental construct if compared to the group that received commercial vaccine. An appropriate response to the positive and negative DIVA tags was detected. Therefore, the strategy used in this study is the first to enable a DIVA capable vaccine and accompanying immuno-assay, while using an epitope based approach to target improved immunogenicity.