In the present study, five eukaryotic double-gene expression plasmids containing porcine reproductive and respiratory syndrome virus (PRRSV) ORF5 and ORF7 genes combined with cDNAs encoding porcine IFNgamma and IL-2 were constructed for evaluation as PRRSV vaccine candidates. After immunization and viral challenge, two of three pigs immunized with pIRESorf5/IFNgamma, one of three pigs immunized with pIRESorf5/IL-2 and one of three pigs immunized with pIRESorf7/IL-2 were protected from lung lesions that were present in other vaccinated and control animals. Virus replication was reduced but not completely prevented in organs of the DNA-vaccinated animals as compared to controls. Therefore, the porcine cytokines IFNgamma and IL-2, delivered in combination with ORF5 or ORF7, may improve the immune efficacy of DNA vaccines against PRRSV.