Enhanced immunogenicity of the modified GP5 of porcine reproductive and respiratory syndrome virus

The ORF5-encoded major envelope glycoprotein (GP5) is one of the key immunogenic proteins of the porcine reproductive and respiratory syndrome virus (PRRSV) and is the leading target for the development of the new generation of vaccines against PRRS. However, weak and tardy neutralizing antibodies have been elicited in several developed experimental vaccines expressing PRRSV GP5. More recent evidence has demonstrated a non-neutralizing decoy epitope upstream of the neutralizing epitope of GP5, which might prevent the development of a strong neutralizing antibody response against PRRSV. In the present study, we modified the ORF5 gene by inserting a Pan DR T-helper cell epitope (PADRE) between the neutralizing epitope and the decoy epitope to minimize or eliminate the decoy effect of the non-neutralizing epitope. The immunogenicity of the modified GP5 was further evaluated using DNA vaccination. The results showed that significantly enhanced neutralizing antibodies were elicited in mice immunized with the DNA construct expressing the modified GP5 compared with the native GP5. Slightly increased levels of GP5-specific ELISA antibodies and T-cell proliferative activities were also observed. These results indicate that the high immunogenicity of the modified GP5 might facilitate the development of improved PRRS vaccines in the future.