ANTIBODY RESPONSE OF NEONATES TO MATERNAL IMMUNITY, ACTIVE IMMUNIZATION, HORMONES

研究肺炎球菌多糖免疫的效果 (PS)对新生儿随后对 PS抗原，雌性小鼠给予不同剂量，范围从0.5至50 %g或更多的肺炎球菌多糖，例如19 A、19 F或3 PS型， 在交配之前。 出生后，幼鼠被分成两组。 一组在两周龄时给予额外剂量的PS（0.1%g）。 PS处理过的雌性小鼠所生的幼鼠， 接受额外剂量PS的患者的抗体反应比 那些没有接受额外剂量的PS的人。 治疗 500%g的雌性小鼠诱导抗体应答抑制 在母鼠和幼鼠中。 来自接受激素治疗的母亲的年轻小鼠，如生长 激素或雌激素，然后在怀孕期间接种肺炎球菌疫苗， 对19 A PS产生较高的IgM抗体应答。 GRANTZ01BA02020 用灭活的肺炎球菌溶血素（ply）免疫小鼠已被证明 以增加用强毒肺炎球菌攻击后的存活时间。 因此，灭活的层片可以作为一种有效的蛋白载体， 肺炎球菌多糖（PS）-蛋白质缀合物免疫原。 灭活的1型肺炎球菌溶血素，从E. coli克隆pJCP 20， 通过溴化氰与肺炎球菌19 F PS结合 活化PS和碳二亚胺偶联方法进行缀合。 30- 50%蛋白质包含在19 F PS-蛋白质缀合物中。 19 F PS-ply缀合物的抗体应答通过以下测量： 放射免疫测定 从0.5至50 mg的各种剂量的缀合物被施用。 注射到8周龄的小鼠中。 5 mg的加强注射是 初次给药后7天给药一次，或初次给药后7天和14天给药两次 注射 最后一次注射后7天， 测定了 结果表明，该偶联免疫原诱导了 小鼠中的19 F Ab水平显著高于用 19F PS。 接受两次加强注射的小鼠中的19 F Ab水平 比接受19 F的对照组增加了20倍以上 PS单独 肺炎球菌溶血素的抗体应答和对肺炎球菌攻击的保护作用 将在接受19 F PS-ply的小鼠中测定毒性肺炎球菌 共轭

To study the effect of immunization with pneumococcal polysaccharide (PS) before pregnancy on the subsequent antibody response of neonates to PS antigens, female mice were given various doses ranging from 0.5 to 50 %g or more of pneumococcal polysaccharides, e.g. type 19A, 19F or 3 PS, before mating. After birth the young mice were divided into two groups. One group was given an additional dose of PS (0.1 %g) at two wks of age. The young mice that were born to PS-treated female mice and that received an additional dose of PS had stronger antibody response than those that did not receive an additional dose of PS. Treatment of female mice with 500 %g induced a suppression of the antibody response in maternal and young mice. Young mice from mothers that received hormone treatment, such as growth hormone, or estrogen followed by pneumococcal vaccine during pregnancy, produced higher IgM antibody responses to 19A PS. GRANTZ01BA02020 Immunization of mice with inactivated pneumolysin (ply) has been shown to increase the survival time after challenge with virulent pneumococci. Thus, inactivated ply can serve as an effective protein carrier for pneumococcal polysaccharide (PS)-protein conjugate immunogens. Inactivated type 1 pneumolysin, prepared from E. coli clone pJCP20 was conjugated to pneumococcal type 19F PS by the cyanogen bromide activation of PS and carbodiimide coupling method for conjugation. 30- 50% protein was contained in the 19F PS-protein conjugate. The antibody response of 19F PS-ply conjugate was measured by radioimmuno-assay. Various doses of conjugate from 0.5 to 50 mg were injected into mice at 8 wks of age. A booster injection of 5 mg was given either once at 7 days, or twice at 7 and 14 days after primary injection. Seven days after last injection the antibody response was measured. The results showed that the conjugate immunogen induced significantly higher 19F Ab levels in the mice than were obtained with 19F PS. The 19F Ab levels in mice that received two booster injections were incresed more than 20 fold over the control group that received 19F PS alone. The antibody response to pneumolysin and protection against challenge of virulent pneumococci will be determined in mice receiving 19F PS-ply conjugate.