The U.S pork industry produces an estimated 2.2 metric tons of pork annually, valued at $23.4 billion, of which 26% is exported to other countries (queck-matzie, 2019)

Despite significant growth, pork production continues to be hampered by viruses, such as PCV2, with rapid evolution and high levels of genetic and antigenic variation. As new strains emerge, the relevance of existing vaccines is lost (constans, 2015; meng, 2012). The primary goals of this proposal are (1) to develop an improved PCV2 vaccine candidate that stimulates broadened protective immunity and (2) to assess the accuracy of a novel bioinformatic tool (ANATOPE) in the design of immune refocused vaccines. Our proposed work is concerned with improving our nation's food security and animal health and wellbeing. Current PCV2 vaccines stimulate protective immunity to PCV2A and 2B serotypes but reduced protection against evolving and emerging strains such as PCV2D, 2G, and 2H. We propose to use immune refocusing technology (IRT) to reduce the immunogenicity of epitopes that stimulate subtype-restricted immunity and refocus towards more broadly protective epitopes. Our first-generation IRT candidate demonstrated improved protection against PCV2D compared to a commercially available vaccine. We have designed two second-generation candidates to increase the breadth of protection towards additional subtypes. The vaccine candidates are based on an attenuated strain which will reduce the cost of the vaccines and include a marker epitope for distinguishing between immunized and infected swine. The project will be led by long-time collaborators at biological mimetics, INC. And ndsu. BMI will design the IRT candidates and perform serological analyses of swine sera including cross-neutralization of PCV2D, 2G, and 2H viruses. DR. Ramamoorthy at ndsu will produce the recombinant viruses and the challenge stocks. DR. Pillai at sdsu will perform the swine immunization and challenge experiment and analyze tissues by pathology and histopathology. We aim to identify an improved PCV2 vaccine that stimulates broadened cross-subtype protection that can be further developed in a phase II project.