Ala'Aldeen D A, Stevenson P, Griffiths E, Gorringe A R, Irons L I, Robinson A, Hyde S, Borriello S P
Department of Microbiology, Queen's Medical Centre, Nottingham, United Kingdom.
Infect Immun. 1994 Jul;62(7):2984-90. doi: 10.1128/iai.62.7.2984-2990.1994.
The results reported here show that the two meningococcal transferrin-binding proteins (TBP1 and TBP2) generate different immune responses in different host species and that there is variation in response dependent on the method of antigen preparation and possibly the route of administration. Mice immunized with either whole cells of Neisseria meningitidis SD (B:15:P1.16) or the isolated TBP1-TBP2 complex from the same strain produced antisera which, when tested against a representative panel of meningococcal isolates by Western blotting (immunoblotting), recognized some but not all heterologous TBP2 molecules. In contrast, rabbit antisera raised to the same preparations were cross-reactive with almost all the TBP2 molecules. The immune response to TBP1 was also host species dependent. Western blot analysis with denatured TBP1 failed to detect antibodies in antisera raised in mice to whole cells or in a rabbit to the TBP1-TBP2 complex but detected broadly cross-reactive antibodies in mouse anti-TBP1-TBP2 complex sera and strain-specific antibodies in rabbit anti-whole-cell serum. Human convalescent-phase sera obtained from five patients infected with meningococci of different serogroups and serotypes contained fully cross-reactive antibodies to TBP2 but no anti-TBP1 antibodies, when examined on Western blots. However, on dot immunoblots, the same patients' sera, as well as the mouse anti-whole cell and the rabbit anti-TBP1-TBP2 complex sera, reacted with purified biologically active TBP1 of strain SD. This indicates that native TBP1, a protein which loses its biological and some of its immunological activities when denatured, is immunogenic and that humans generate cross-reactive antibodies to native epitopes. These observations have important implications for assessing the vaccine potential of TBPs and other meningococcal antigens. Conclusions regarding the usefulness of TBPs as candidate components of meningococcal serogroup B vaccines based on results from certain animal species such as mice, or on methods such as Western blotting, may have little bearing on the situation in humans and may lead to some potentially useful antigens being disregarded.
此处报告的结果表明，两种脑膜炎球菌转铁蛋白结合蛋白（TBP1和TBP2）在不同宿主物种中产生不同的免疫反应，并且反应存在差异，这取决于抗原制备方法以及可能的给药途径。用脑膜炎奈瑟菌SD（B:15:P1.16）全细胞或从同一菌株分离的TBP1 - TBP2复合物免疫的小鼠产生了抗血清，当通过蛋白质印迹法（免疫印迹）针对一组代表性的脑膜炎球菌分离株进行检测时，该抗血清识别了部分但不是全部的异源TBP2分子。相比之下，用相同制剂产生的兔抗血清与几乎所有的TBP2分子发生交叉反应。对TBP1的免疫反应也取决于宿主物种。用变性TBP1进行的蛋白质印迹分析未能在小鼠全细胞抗血清或兔TBP1 - TBP2复合物抗血清中检测到抗体，但在小鼠抗TBP1 - TBP2复合物血清中检测到广泛交叉反应的抗体，在兔抗全细胞血清中检测到菌株特异性抗体。从五名感染不同血清群和血清型脑膜炎球菌的患者获得的人类恢复期血清在蛋白质印迹检测时含有对TBP2完全交叉反应的抗体，但没有抗TBP1抗体。然而，在斑点免疫印迹中，相同患者的血清以及小鼠抗全细胞血清和兔抗TBP1 - TBP2复合物血清与菌株SD的纯化生物活性TBP1发生反应。这表明天然TBP1（一种变性时会失去其生物学和部分免疫活性的蛋白质）具有免疫原性，并且人类会产生针对天然表位的交叉反应抗体。这些观察结果对于评估TBP和其他脑膜炎球菌抗原的疫苗潜力具有重要意义。基于某些动物物种（如小鼠）的结果或蛋白质印迹等方法得出的关于TBP作为B群脑膜炎球菌疫苗候选成分有用性的结论，可能与人类情况关系不大，并且可能导致一些潜在有用的抗原被忽视。
