Department of Veterinary and Animal Sciences, University of Copenhagen, Stigbøjlen 4, 1870 Frb. C., 1-20, Building: 301, Copenhagen, Denmark.
Department of International Health, Immunology and Microbiology ISIM, University of Copenhagen, Øster Farigmagsgade 5, Bldg 22/23, 1014 København K, Copenhagen, Denmark.
Vet Res. 2018 Jan 9;49(1):4. doi: 10.1186/s13567-017-0502-x.
Actinobacillus pleuropneumoniae (A. pleuropneumoniae) is a Gram-negative bacterium that represents the main cause of porcine pleuropneumonia in pigs, causing significant economic losses to the livestock industry worldwide. A. pleuropneumoniae, as the majority of Gram-negative bacteria, excrete vesicles from its outer membrane (OM), accordingly defined as outer membrane vesicles (OMVs). Thanks to their antigenic similarity to the OM, OMVs have emerged as a promising tool in vaccinology. In this study we describe the in vivo testing of several vaccine prototypes for the prevention of infection by all known A. pleuropneumoniae serotypes. Previously identified vaccine candidates, the recombinant proteins ApfA and VacJ, administered individually or in various combinations with the OMVs, were employed as vaccination strategies. Our data show that the addition of the OMVs in the vaccine formulations significantly increased the specific IgG titer against both ApfA and VacJ in the immunized animals, confirming the previously postulated potential of the OMVs as adjuvant. Unfortunately, the antibody response raised did not translate into an effective protection against A. pleuropneumoniae infection, as none of the immunized groups following challenge showed a significantly lower degree of lesions than the controls. Interestingly, quite the opposite was true, as the animals with the highest IgG titers were also the ones bearing the most extensive lesions in their lungs. These results shed new light on A. pleuropneumoniae pathogenicity, suggesting that antibody-mediated cytotoxicity from the host immune response may play a central role in the development of the lesions typically associated with A. pleuropneumoniae infections.
胸膜肺炎放线杆菌（A. pleuropneumoniae）是一种革兰氏阴性菌，是导致猪传染性胸膜肺炎的主要病原体，给全球畜牧业造成了巨大的经济损失。与大多数革兰氏阴性菌一样，A. pleuropneumoniae 从其外膜（OM）中分泌出囊泡，因此被定义为外膜囊泡（OMVs）。由于其与 OM 的抗原相似性，OMVs 已成为疫苗学中的一种有前途的工具。在本研究中，我们描述了几种预防所有已知 A. pleuropneumoniae 血清型感染的疫苗原型的体内测试。先前鉴定的疫苗候选物，重组蛋白 ApfA 和 VacJ，单独或与 OMVs 以各种组合形式给药，被用作疫苗接种策略。我们的数据表明，在疫苗配方中添加 OMVs 显著增加了免疫动物针对 ApfA 和 VacJ 的特异性 IgG 滴度，证实了 OMVs 作为佐剂的先前假设的潜力。不幸的是，所产生的抗体反应并没有转化为对 A. pleuropneumoniae 感染的有效保护，因为在挑战后，没有一个免疫组的病变程度明显低于对照组。有趣的是，情况恰恰相反，因为 IgG 滴度最高的动物肺部的病变也最广泛。这些结果为 A. pleuropneumoniae 的致病性提供了新的见解，表明宿主免疫反应的抗体介导的细胞毒性可能在与 A. pleuropneumoniae 感染相关的病变的发展中起核心作用。
