Interference of outer membrane protein PalA with protective immunity against Actinobacillus pleuropneumoniae infections in vaccinated pigs

Abstract

The role of antibodies to the outer membrane protein PalA of Actinobacillus pleuropneumoniae in protective immunity was studied in pigs vaccinated with purified PalA alone and PalA in combination with toxoids of the RTX toxins ApxI and ApxII using an established challenge model with the virulent serotype 1 of A. pleuropneumoniae. Pigs that developed antibody titers against PalA after immunization were more significantly affected by challenge with A. pleuropneumoniae serotype 1. Following challenge, pigs that were immunized with PalA showed more severe respiratory symptoms, had a higher mortality rate and died faster. They also displayed much more severe lung lesions after necropsy than animals not immunized with PalA. Pigs that were immunized with toxoids of the two cytotoxins ApxI and ApxII were protected against challenge with A. pleuropneumoniae. In contrast, the protective efficacy of the ApxI and ApxII vaccine was completely lost when it was supplemented with PalA. Hence, antibodies induced against the outer membrane protein PalA of A. pleuropneumoniae aggravated the consequences of infection and counteracted the protective effect of anti-ApxI and anti-ApxII antibodies. Due to the high similarity between protein analogues of PalA from various bacteria of the Pasteurellaceae family such as P6 of Haemophilus influenzae or 16kDa Omp of Pasteurella multocida, this deleterious effect of PalA in vaccination should be taken into consideration in the development of vaccines against infections with other Pasteurellaceae.