The current vaccines against PRRSV protect pigs exposed to the strain used to make the vaccine, but not to the many field strains that herds encounter. The lack of protection against heterologous challenge may be caused by genetic variability of the virus and by dysregulating epitopes (portions of the virus against which the host immune system reacts) on the virus that misdirect the pig immune system. We have applied our immune refocusing technique to improve protection against many strains of PRRSV. Thus, we have attempted to redirect the immune system away from strain-specific or non-protective portions of the virus (decoy epitopes on GP5) and towards parts of the virus that were previously hidden yet may induce broader protection. To test this method, we engineered recombinant vaccinia viruses that express two sets of mutated GP5 glycoproteins and then used these viruses to immunize laboratory animals. Some of the modified GP5 glycoproteins induced higher levels of neutralizing activity and suggest that the immune refocusing technology may result in improved PRRS vaccines. We have submitted a follow-up proposal designed to investigate these mutations in the context of an existing PRRS vaccine strain. These studies would lead to second-generation vaccines which may be capable of broadened protection against multiple strains of PRRSV.