Leibl H, Tomasits R, Eibl M M, Mannhalter J W
Department of Immunological Research, Immuno AG, Vienna, Austria.
Vaccine. 1998 Feb;16(4):340-5. doi: 10.1016/s0264-410x(97)80911-5.
Virus-like or virus-derived particles have been reported to increase the immunogenicity of foreign antigens. In this study formaldehyde-inactivated tick-borne encephalitis virus (TBEV), a potent immunogen in humans, was tested for possible adjuvant/carrier function. The results of our study revealed that substantial antibody titers against very low doses of tetanus toxoid could be obtained when mice were immunized with the antigen covalently coupled to TBEV (using N-succinimidyl-3-(2-pyridyldithio)propionate, a heterobifunctional, cleavable crosslinker containing a disulfide bridge). In contrast, only moderate anti-tetanus toxoid titers were induced by immunizations with a simple mixture of low dose tetanus toxoid and TBEV or when the disulfide bridge of the crosslinker used to couple tetanus toxoid to TBEV was cleaved prior to immunization. The antibody response to TBEV, on the other hand, was not influenced by its linkage to tetanus toxoid. Comparable anti-TBEV titers were obtained following immunization of the animals with either the TBEV-tetanus toxoid conjugate or the mixture of tetanus toxoid and TBEV. Prior application of a TBEV vaccine did not change the antibody response against tetanus toxoid and thus carrier-induced epitopic suppression could be ruled out. The abovementioned adjuvant/carrier properties of TBEV might make it a suitable candidate for use in bi- or multivalent vaccines containing weak immunogens.
据报道，病毒样颗粒或病毒衍生颗粒可增强外源抗原的免疫原性。在本研究中，对人强效免疫原甲醛灭活蜱传脑炎病毒（TBEV）的潜在佐剂/载体功能进行了测试。我们的研究结果显示，当用与TBEV共价偶联的抗原（使用N-琥珀酰亚胺基-3-（2-吡啶二硫基）丙酸酯，一种含二硫键的异双功能可裂解交联剂）免疫小鼠时，针对极低剂量破伤风类毒素可获得高抗体滴度。相比之下，用低剂量破伤风类毒素和TBEV的简单混合物免疫，或在免疫前裂解用于将破伤风类毒素偶联至TBEV的交联剂的二硫键时，仅诱导出中等抗破伤风类毒素滴度。另一方面，对TBEV的抗体反应不受其与破伤风类毒素连接的影响。用TBEV-破伤风类毒素偶联物或破伤风类毒素与TBEV的混合物免疫动物后，获得了相当的抗TBEV滴度。预先接种TBEV疫苗并未改变针对破伤风类毒素的抗体反应，因此可以排除载体诱导的表位抑制。TBEV上述的佐剂/载体特性可能使其成为含有弱免疫原的二价或多价疫苗的合适候选物。
