Abstract
Porcine infectious pleuropneumonia (PCP) caused by Actinobacillus pleuropneumoniae (APP) leads to severe economic losses in swine production. Commercial vaccines offer limited cross-protection for the 19 serotypes, while APP mRNA vaccines remain unexplored. This study evaluated eight candidate APP proteins (ApxI-IV, OlmA, TbpB, GalT, and GalU) using immunobioinformatics tools, and their immunogenicity and cross-protection were assessed in a mouse model. The results revealed that ApxI and ApxII excel due to their stability, strong antigenicity, non-sensitization, and high immune receptor affinity. Compared to the PBS group, both ApxI and ApxII induced higher serum IgG, IL-2, IL-4, and IFN-γ levels. Following challenge with the two most prevalent APP strains in Mainland China, APP 5b and APP 1, the survival rates for ApxI (71.4% and 62.5%) and ApxII (75% and 71.4%) were measured, with notably reduced lung lesions and neutrophil infiltration. These findings highlight ApxI and ApxII's potential in mRNA vaccine development as a promising approach to overcome current vaccine limitations. Future research should focus on creating APP mRNA vaccines and testing their efficacy in swine. This study is the first to combine immunoinformatics with experimental validation for APP mRNA vaccine antigens, representing a novel contribution.