Porcine reproductive and respiratory syndrome (PRRS) is one of the most important diseases of domestic swine. The etiologic agent is a virus (PRRSV), and has proven to be a difficult target for control and eradication efforts. Therefore, it is desirable to develop an improved generation of PRRS vaccines to address these and other shortcomings. Alphavirus-derived replicon particle (RP) vaccines have demonstrated efficacy and safety in a wide range of disease and animal models. Recently, an RP platform derived from Venezuelan equine encephalitis virus (strain, TC-83) was developed for use in veterinary vaccines, including vaccines for swine. The key attributes of this technology are that RPs are propagation-defective, single-cycle RNA virus vectors, and are capable of eliciting potent humoral and cellular immune responses to a wide variety of antigens. In these studies, RP were used to express PRRSV proteins GP3, GP4, GP5, and M as vaccine antigens in young pigs. Vaccinated animals developed specific humoral and cellular immune responses, and also had reduced viremia and viral load post-challenge. Similar vaccine candidates were evaluated in pregnant gilts, but no significant reduction in disease were observed compared to controls. Additionally, an RP influenza vaccine administered 24 hours prior to PRRSV challenge reduced viremia and viral load in young pigs compared to controls. This effect was independent of PRRSV-derived antigens, highlighting the utility of the RP to investigate the host immune response to viral infection. Overall, these data demonstrate that RP represent a powerful tool for future PRRS vaccine research and disease control efforts.