van den Bosch Han, Frey Joachim
Intervet International, P.O. Box 31, NL-5830 AA, Boxmeer, The Netherlands.
Vaccine. 2003 Sep 8;21(25-26):3601-7. doi: 10.1016/s0264-410x(03)00410-9.
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.
利用已建立的胸膜肺炎放线杆菌强毒血清型1攻毒模型,研究了单独用纯化的PalA以及PalA与RTX毒素ApxI和ApxII类毒素联合免疫的猪中,抗胸膜肺炎放线杆菌外膜蛋白PalA的抗体在保护性免疫中的作用。免疫后产生抗PalA抗体效价的猪,受到胸膜肺炎放线杆菌血清型1攻毒的影响更显著。攻毒后,用PalA免疫的猪表现出更严重的呼吸道症状和更高的死亡率,死亡更快。尸检后,它们的肺部病变也比未用PalA免疫的动物严重得多。用两种细胞毒素ApxI和ApxII类毒素免疫的猪对胸膜肺炎放线杆菌攻毒具有保护作用。相反,当ApxI和ApxII疫苗中添加PalA时,其保护效力完全丧失。因此,诱导产生的抗胸膜肺炎放线杆菌外膜蛋白PalA的抗体加重了感染后果,并抵消了抗ApxI和抗ApxII抗体的保护作用。由于巴斯德菌科各种细菌的PalA蛋白类似物之间高度相似,如流感嗜血杆菌的P6或多杀巴斯德菌的16kDa Omp,在开发针对其他巴斯德菌科感染的疫苗时,应考虑PalA在疫苗接种中的这种有害作用。