Oral immunization of mice with ricin toxoid vaccine encapsulated in polymeric microspheres against aerosol challenge
Oral immunization of mice with ricin toxoid vaccine encapsulated in polymeric microspheres against aerosol challenge
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DOI：
10.1016/s0264-410x(01)00484-4
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发表时间：
2002-02-22
期刊：
影响因子：
5.5
通讯作者：
Tammariello, R
中科院分区：
文献类型：
--
作者：
Kende, M;Yan, CH;Tammariello, R
通过一个长（7周）或两个短（4周）的免疫接种计划，完成用载体递送的蓖麻毒素类毒素（RT）疫苗对小鼠的粘液（口服）免疫。对于长期和短期免疫接种计划，使用相同程序但在不同时间接种两批疫苗。长期方案包括在第1、2、3、28、29、30和49天给予总共7剂50 μ g微囊化（批号108）或水性形式的疫苗。在短时间方案中，分别在第1、2、3、14、15、16和30天，或在第1、2、14、15、30、31和32天，共给予7或6剂25 μ g（批号111）。用长时间口服免疫小鼠，50 μ g掺入聚-DL-丙交酯-共-乙交酯（DL-PLG）微球（MS）的RT疫苗产生血清IgG、IgG 2a和I-A ELISA抗体。所有在DL-PLG MS（RT-MS）中用RT免疫的小鼠均受到保护，免受致死性蓖麻毒素气溶胶攻击。相比之下，在相同的时间表和相同的剂量下，水性疫苗（RT）未能刺激IgG，IgG 2a和伊加抗体，并且这些小鼠不能抵抗气溶胶蓖麻毒素攻击。在较短的免疫方案中，7个剂量的25 Rg RT-MS刺激了微囊化疫苗的显著保护作用，但保护作用降低，而水性疫苗则没有。当第一个和第二个3天周期的短免疫接种时间表减少到两个剂量，并在该时间表结束时给予3天周期时，RT-MS和RT都不能刺激针对攻击的保护。这些结果表明，成功的口服免疫与RT-MS依赖于剂量和时间表，包括连续三天的两个周期，间隔4周的管理。改变这个时间表和剂量，导致保护减少或根本没有保护。此外，在本研究的条件下，充分证明了微囊化RT疫苗在有效口服免疫方面优于水性疫苗。(C)2002爱思唯尔科技有限公司版权所有。
Mucosal (oral) immunization of mice with carrier-delivered ricin toxoid (RT) vaccine was accomplished by one long (7 weeks) or two short (4 weeks) immunization schedules. For the long and short immunization schedule two lots of vaccine were administered prepared with the same procedure but at different occasions. The long schedule consisted of a total of seven doses of 50 mug of vaccine in microencapsulated (lot #108) or aqueous form administered on days 1, 2, 3, 28, 29, 30 and 49. With the short schedule a total of seven or six doses of 25 mug (lot #111) were administered on days 1, 2, 3, 14, 15, 16 and 30, or on 1, 2, 14, 15, 30, 31 and 32, respectively. Mice immunized orally with the long schedule, 50 mug of RT vaccine incorporated into poly-DL-lactide-co-glycolyde (DL-PLG) microspheres (MS) produced serum IgG, IgG2a and I-A ELISA antibodies. All mice immunized with RT in DL-PLG MS (RT-MS) were protected against a lethal ricin aerosol challenge. In contrast, with the same schedule and with the same dose, the aqueous vaccine (RT) failed to stimulate IgG, IgG2a and IgA antibodies, and these mice were not protected against an aerosol ricin toxin challenge. With the shorter immunization scheme, seven doses of 25 Rg RT-MS stimulated a significant, though reduced, protection with the microencapsulated, but not with the aqueous vaccine. When the first and second 3-day cycles of the short immunization schedule was reduced to two doses, and the 3-day cycle was administered at the end of the schedule, neither RT-MS nor RT stimulated protection against the challenge. These results indicated that successful oral immunization with RT-MS depended on both the dose and the schedule, consisting of three consecutive days of administration in two cycles, 4 weeks apart. Altering this schedule and the dose, resulted in a reduced protection or no protection at all. Furthermore, under the conditions of this study, the advantage of the microencapsulated RT vaccine over the aqueous vaccine for effective oral immunization was well demonstrated. (C) 2002 Elsevier Science Ltd. All rights reserved.