Establishment of Immune Biobank for Vaccine Immunogenicity Prediction Using <em>In Vitro</em> and <em>In Silico</em> Methods Against Porcine Reproductive and Respiratory Syndrome Virus

Background/Objectives: Porcine reproductive and respiratory syndrome virus (PRRSV) remains one of the most economically significant pathogens in the global swine industry. Despite the availability of commercial vaccines for over three decades, they fail to induce sterile immunity and often provide inconsistent protection against heterologous PRRSV strains. This study aimed to predict vaccine immunogenicity by detecting strain-specific immune responses that related to an immune correlates of protection (COPs) against different PRRSV-2 strains. Methods: Post-weaning pigs were vaccinated with five commercially available PRRSV-2 vaccines or received sterile PBS injection as a control. At 28 days post-vaccination (dpv), all pigs were humanely euthanized for large-volume blood collection to isolate peripheral blood mononuclear cells (PBMCs) and plasma, establishing the immune bank. PBMCs and plasma from each group were then tested against six PRRSV-2 strains to evaluate immune responses. In addition, T cell epitope coverage between vaccine and field PRRSV-2 strains was assessed using the EpiCC (in silico) tool to enhance predictive capacity. Results: While neutralizing antibodies were undetectable in all vaccinated pigs at 28 dpv, PRRSV-specific IFNg–producing cells were detected at various levels in each vaccinated group following restimulation with different PRRSV-2 strains. Additionally, a positive correlation was observed for the EpiCC coverage of the N gene and mean IFNg responses to VR2332 (SLA class I and II) and NC24-6 (SLA class II). Conclusions: The PRRSV immune bank demonstrated potential as a tool for predicting vaccine immunogenicity against different PRRSV-2 strains and EpiCC provide additional information on T cell epitope cross conservation. The combined approach may provide a valuable framework for selecting PRRSV vaccines for more effective prevention and control in endemic areas.