Yan C, Rill W L, Malli R, Hewetson J, Naseem H, Tammariello R, Kende M
United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, MD 21702-5011, USA.
Vaccine. 1996 Aug;14(11):1031-8. doi: 10.1016/0264-410x(96)00063-1.
Intranasal (i.n.) immunization with ricin toxoid (RT) vaccine encapsulated in poly (lactide-co-glycolide) microspheres (RT-PLG-Ms) and poly (L-lactide) microspheres (RT-PLA-Ms) stimulated systemic and mucosal immune responses and protected mice from aerosolized ricin intoxication. High titers of anti-ricin IgG2a were stimulated in the serum of mice with one or two doses of RT-Ms 6 weeks postimmunization. However, in the lungs, no IgG2a or total IgG was elicited either with RT-Ms or with aqueous RT. At 6 weeks postimmunization, a single dose of the RT-Ms stimulated secretory IgA (sIgA) in the lungs of four of six mice, but a second immunizing dose did not enhance the stimulation. A single dose of aqueous RT vaccine failed to stimulate sIgA in the lungs, while, a second dose induced sIgA in 50% of the mice. One or two i.n. doses of RT-Ms protected most of the mice against lethal aerosol-delivered ricin toxin 6 weeks postimmunization. In contrast, protection was absent or marginal after one or two doses of aqueous RT vaccine. In both studies, the protection against lethal aerosol challenge was significantly better with one dose of RT-Ms than with two doses of aqueous vaccine, which may be attributed to the induction of sIgA in the lungs and the serum. Duration of the IgG2a and IgA in the serum, particularly that of IgG2a was much longer after the administration of RT-Ms than after the aqueous vaccine. The geometric mean IgG2a titers stimulated with two doses of RT-Ms remained high during 40 weeks postimmunization and were up to 25 times higher than the titers induced with aqueous RT vaccine. After 6 weeks, the IgG2a induced by two doses of aqueous vaccine was no longer detectable. Persistence of antibody response was predictive of efficacy. At 1 year postimmunization with two doses of RT-Ms, 100% of mice were protected against lethal ricin challenge. However, at the same time no protection was afforded by two doses of aqueous RT. The results of the present study consistently demonstrated the advantages of microencapsulated RT vaccine to stimulate effective and long-lasting protection by i.n. administration.
用包裹在聚（丙交酯 - 乙交酯）微球（RT - PLG - Ms）和聚（L - 丙交酯）微球（RT - PLA - Ms）中的蓖麻毒素类毒素（RT）疫苗进行鼻内（i.n.）免疫，可刺激全身和黏膜免疫反应，并保护小鼠免受雾化蓖麻毒素中毒。在免疫后6周，用一剂或两剂RT - Ms免疫的小鼠血清中刺激产生了高滴度的抗蓖麻毒素IgG2a。然而，在肺部，RT - Ms或水性RT均未引发IgG2a或总IgG。在免疫后6周，一剂RT - Ms刺激了六只小鼠中的四只肺部产生分泌型IgA（sIgA），但第二剂免疫并未增强这种刺激。一剂水性RT疫苗未能刺激肺部产生sIgA，而第二剂在50%的小鼠中诱导产生了sIgA。一剂或两剂鼻内RT - Ms在免疫后6周保护了大多数小鼠免受致死性气溶胶递送的蓖麻毒素毒素的侵害。相比之下，一剂或两剂水性RT疫苗后没有保护作用或保护作用微弱。在两项研究中，一剂RT - Ms对致死性气溶胶攻击的保护作用明显优于两剂水性疫苗，这可能归因于肺部和血清中sIgA的诱导。RT - Ms给药后血清中IgG2a和IgA的持续时间，特别是IgG2a的持续时间比水性疫苗给药后长得多。两剂RT - Ms刺激产生的几何平均IgG2a滴度在免疫后40周内保持较高水平，比水性RT疫苗诱导的滴度高出25倍。6周后，两剂水性疫苗诱导的IgG2a不再可检测到。抗体反应的持久性可预测疗效。在两剂RT - Ms免疫后1年，100%的小鼠受到保护，免受致死性蓖麻毒素攻击。然而，与此同时，两剂水性RT没有提供保护作用。本研究结果一致证明了微囊化RT疫苗通过鼻内给药刺激产生有效和持久保护的优势。
