Griffiths G D, Bailey S C, Hambrook J L, Keyte M P
Medical Countermeasures Department, Chemical and Biological Defence, Porton Down, Salisbury, Wiltshire, UK.
Vaccine. 1998 Mar;16(5):530-5. doi: 10.1016/s0264-410x(97)80007-2.
The objective of this study was to develop a vaccine which would ultimately protect man from the lethal effects of inhaled ricin toxin. Porton rats have previously been protected from lethal quantities of inhaled ricin by subcutaneous (s.c.) ricin toxoid vaccine, but not without lung damage. This situation might be improved by an alternative vaccine such as the A chain of ricin, already known to protect against inhaled ricin. Another option would be to improve respiratory tract immunity by local vaccination in conjunction with liposomal formulation with a view to enhancing lung secretion of immune IgA. While boosted s.c. doses of ricin toxoid or A chain produced indistinguishable systemic immune responses 3 weeks later, when delivered by the intratracheal (i.t.) route, the A chain failed to elicit a specific immune response, unlike ricin toxoid. This situation was overcome by liposomal formulations and although ricin toxoid was readily encapsulated in liposomes, A chain was not. However, by simply mixing A chain and liposomes in the same weight ratio determined for liposomal toxoid, systemic immune responses for each formulation were indistinguishable 1 week after boosting. Ricin antibody responses in lung fluid monitored 1, 3, 7 and 14 days after i.t. challenge with ricin were statistically indistinguishable, but the group vaccinated with liposomal toxoid secreted 28.7% IgA compared with 0.9-14.9% for the A chain liposomal group. From this, it might be anticipated that the lungs would be better protected by liposomally-encapsulated ricin toxoid than by the A chain-liposome mixture.
本研究的目的是研发一种最终能保护人类免受吸入型蓖麻毒素致命影响的疫苗。此前，皮下注射蓖麻类毒素疫苗可使波顿大鼠免受致死剂量的吸入型蓖麻毒素侵害，但会造成肺部损伤。一种替代疫苗，如已知可预防吸入型蓖麻毒素的蓖麻毒素A链，可能会改善这种情况。另一种选择是通过局部接种结合脂质体制剂来增强呼吸道免疫力，以提高肺部免疫球蛋白A的分泌。虽然皮下注射加强剂量的蓖麻类毒素或A链在3周后产生的全身免疫反应难以区分，但通过气管内给药时，与蓖麻类毒素不同，A链未能引发特异性免疫反应。脂质体制剂克服了这一情况，尽管蓖麻类毒素很容易被包封在脂质体中，但A链却不行。然而，只需将A链和脂质体按脂质体类毒素确定的相同重量比混合，加强免疫1周后，每种制剂的全身免疫反应就难以区分。在气管内注射蓖麻毒素后1、3、7和14天监测肺液中的蓖麻毒素抗体反应，结果在统计学上无显著差异，但接种脂质体类毒素的组分泌的免疫球蛋白A为28.7%，而A链脂质体组为0.9 - 14.9%。由此可以预期，脂质体包封的蓖麻类毒素对肺部的保护作用要优于A链 - 脂质体混合物。
