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Actinobacillus pleuropneumoniae  ( A. pleuropneumoniae/APP ) is the pathogen that causes porcine contagious pleuropneumonia.  Actinobacillus pleuropneumoniae  is divided into 18 serovars, and the cross protection efficacy of epitopes is debatable, which has resulted in the slow development of a vaccine. Consequently, epitope-based vaccines conferring  Actinobacillus pleuropneumoniae  cross protection have rarely been reported. In this study, B cell epitopes in the head domain of trimeric autotransporter adhesin were predicted, and 6 epitopes were selected. Then, the predicted epitopes (Ba1, Bb5, C1, PH1 and PH2) were connected by linkers to construct a recombinant tandem antigen ( rta ) gene. The RTA protein encoded by the recombinant  rta  gene was expressed, and finally the ICR mice were immunized with the RTA protein with or without inactivated  Actinobacillus pleuropneumoniae  (serovars 1 and 5b) and challenged with  Actinobacillus pleuropneumoniae  to evaluate the protective effect of the epitope-based vaccine and combined vaccine. The mice in the RTA-immunized group and RTA plus inactivated  Actinobacillus pleuropneumoniae  vaccine group had a significant improvement in clinical symptoms and a higher level of antibody in the serum than those in the control group. The RTA immune group had a 40% survival rate after  Actinobacillus pleuropneumoniae  infection, whereas the combination of RTA and inactivated  Actinobacillus pleuropneumoniae  produced very strong cross immune protection in mice, at least 50% (RTA IB1 + C5) and at most 100% (RTA IB5 + C1), whereas no cross immunoprotection was found in the solo  Actinobacillus pleuropneumoniae  immune group. Overall, the combination of the RTA protein and inactivated bacteria significantly enhanced the cross protection effects. This implies that RTA protein in combination with a suitable inactivated  Actinobacillus pleuropneumoniae  strain could be a candidate vaccine for porcine contagious pleuropneumonia.

Recombinant tandem epitope vaccination provides cross protection against Actinobacillus pleuropneumoniae challenge in mice