Both industry and scientific experts alike agree in that an effective, broadly protective vaccine against PRRS is a very important tool to help in the control of this disease. Our laboratory pursues the overall objective of developing a new, rationally designed vaccine against PRRSV. For a “new generation” vaccine to be successful, it is required that the novel product be broadly protective, which means that the vaccine should be able to confer protection against a vast diversity of PRRSV strains that circulate in the field. The project we report herein was initiated in 2005 and continued in 2008, in both cases with Pork Check-off monies. Through this project we sought a novel way for classifying the repertoire of PRRSV strains. The classification of PRRSV strains that we propose is based on the ability of each strain to induce antibodies in a pig or to react with those antibodies in a test tube. By means of a set of selected reference PRRSV strains and specific antisera prepared against these, we have been able to establish a method that compares and classifies the PRRSV strains in their ability to cross neutralize against each other. By “neutralization” it is understood the ability of antibodies to inactivate PRRSV in a test tube. Based on cross neutralization we have been able to define a number of PRRSV strain clusters or groups that we postulate will have direct relationship with the ability of the strains to protect against each other. Under such notion, we can use this information to define the minimal combination of protective specificities (or “valencies”) that would be required to be contained in a vaccine for this to be broadly protective. This NPB project has permitted, by the first time, to describe the variability of PRRSV strains through an objective, biologically meaningful and immunologically measurable parameter. Until now, variability of PRRSV strains had been defined exclusively in terms of genetic sequencing of a small segment of the PRRSV genome (i.e. the GP5 gene). This latter type of measurement does not relate well to actual protection amongst PRRSV strains. Perhaps the most significant output of this NPB-funded project is that it provided the preliminary results that helped to substantiate a larger scale project (of @ 1million dollar) that PRRSV CAP2 recently awarded to a consortium of 4 universities, amongst which we are included. This larger scale project will center on correlating our immunological characterization of the PRRSV strains with the overall variation of their entire genome and their actual cross-protection in vivo.