Current PRRS vaccines are not adequately effective for control and eradication of PRRS. The main limitation of the current PRRS vaccines is their sub-optimal coverage against divergent PRRSV strains circulating in the field. The substantial genetic variation among the PRRSV strains is the biggest obstacle for the development of a broadly protective PRRS vaccine. Thus far, all commercial PRRS vaccines are formulated using natural PRRSV strains. In this current project, we proposed a novel approach to the development of a PRRSV vaccine strain that could confer broader cross-protection. Specifically, we applied a validated bioinformatics algorithm to design an artificial PRRSV genome based on a large set of full-genome sequences of PRRSV isolates which represent the widest genetic diversity of PRRSV strains circulating in the U.S. swine herds. This artificial PRRSV genome was designed in such a way that it should have the highest degree of genetic similarity to all the PRRSV field-isolates when compared to any natural PRRSV strains. After that, we chemically synthesized this computer-designed PRRSV genome (herein designated as PRRSV-CON) and used reverse genetics techniques to generate a viable PRRSV-CON virus. Our data showed that the PRRSV-CON virus replicates as efficiently as our prototype PRRSV strain FL12, both in cell culture and in pigs. To this end, we conducted two sets of standard cross-protection experiments in pigs to evaluate the cross-protective capacity of the PRRSV-CON virus. Each set of experiments consisted of 3 groups of weaning pigs, 6 pigs per group. Pigs in group 1 served as non-immunization control whereas those in groups 2 and 3 were infected with either with the PRRSV-CON virus or the PRRSV strain FL12. The PRRSV strain FL12 that is closely similar to the parental strain of the Ingelvac PRRS® ATP was used for the comparison purposes. At 52 days post-primary infection, all control and immunized pigs were challenged with a heterologous PRRSV isolate. The results of these experiments showed that the PRRSV-CON confers significantly broader protection than the prototype PRRSV strain FL12. Collectively, our data demonstrate that the PRRSV-CON can serve as a potential vaccine candidate for the development of a novel PRRS vaccine with broader cross-protection.