Laboratory of Microbiology and Advanced Immunology, Faculty of Agronomy and Veterinary Medicine, University of Passo Fundo, Passo Fundo, 99052-900, Brazil.
Department of Microbiology & Infectious Diseases, Faculty of Medicine, University of Calgary, Calgary, T2N 4N1, Alberta, Canada.
Sci Rep. 2017 Sep 4;7(1):10377. doi: 10.1038/s41598-017-10627-0.
Vaccines have become fundamental in the control and elimination of Glässer Disease, a systemic disease of pigs caused by Haemophilus parasuis. The classic vaccines available for prevention of this infection were developed without a robust knowledge about host immunological mechanisms. In this study, we demonstrated the presence of cross-reactive epitopes on both the N-lobe and C-lobe of variants of transferrin binding protein B (TbpBs) expressed on the surface of 6 virulent serovars of H. parasuis. Antibodies against TbpB-derived antigens were capable of increasing the phagocytic capacity of neutrophils and were also capable of blocking porcine transferrin from binding to TbpB. Surprisingly, none of the pig or mice antisera from animals immunized with TbpB-derived antigens mixed with Montanide IMS 2215 VG PR adjuvant were able to activate the classical complement pathway (CCP). In contrast, antisera from mice immunized with TbpB-derived antigens adjuvanted with Freund's adjuvants or Montanide Gel 01 were able to activate the CCP and kill H. parasuis. Our results demonstrate that the type of adjuvant can modulate the functional response induced by TbpB-derived antigens. Based on these results, we propose that a properly formulated TbpB-based vaccine may elicit a functional protective antibody response with broad cross-reactivity against heterologous strains of H. parasuis.
疫苗在控制和消除由副猪嗜血杆菌引起的系统性疾病——格拉泽氏病方面发挥了重要作用。目前用于预防这种感染的经典疫苗是在对宿主免疫机制缺乏深入了解的情况下开发的。在这项研究中，我们证明了在 6 种具有毒力的副猪嗜血杆菌血清型表面表达的转铁蛋白结合蛋白 B（TbpB）的 N 结构域和 C 结构域上存在交叉反应表位。针对 TbpB 衍生抗原的抗体能够增加中性粒细胞的吞噬能力，并且能够阻止猪转铁蛋白与 TbpB 结合。令人惊讶的是，用 TbpB 衍生抗原与 Montanide IMS 2215 VG PR 佐剂混合免疫的动物的猪或小鼠抗血清均不能激活经典补体途径（CCP）。相比之下，用 Freund 佐剂或 Montanide Gel 01 佐剂免疫的 TbpB 衍生抗原免疫的小鼠抗血清能够激活 CCP 并杀死副猪嗜血杆菌。我们的结果表明，佐剂的类型可以调节 TbpB 衍生抗原诱导的功能反应。基于这些结果，我们提出了一种经过适当配方的基于 TbpB 的疫苗，可能会引发针对异源副猪嗜血杆菌菌株具有广泛交叉反应性的功能性保护抗体反应。
