PRECLINICAL SAFETY AND IMMUNOGENICITY OF GROUP B MENINGOCOCCAL VACCINES

B 组脑膜炎球菌疫苗的临床前安全性和免疫原性

• 批准号: 2568873
• 负责人: S DEVI
• 金额: --
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/2568873
• 关键词: Macaca mulatta; Neisseria meningitidis; Neisseria meningitidis vaccine; active immunization; antibacterial antibody; antibody specificity; antigen antibody reaction; bacterial antigens; bacterial capsules; bacterial polysaccharides; bactericidal immunity; drug screening /evaluation; enzyme linked immunosorbent assay; immunoconjugates; nonhuman therapy evaluation

The binding specificity of rhesus antibodies elicited by various conjugate vaccines of group B Neisseria meningitidis (GBNM) was studied using a variety of group B meningococcal polysaccharide (GBPS) antigen systems. The antibody response, as measured by ELISA, was significantly higher to the spacer-containing GBPS or N-propionylated version of GBPS than to the native GBPS complexed with methylated human serum albumin (HSA). The specificity of a population of antibodies directed to the spacer, ADH, was confirmed by their binding to an unrelated pneumococcal 9V polysaccharide conjugated to HSA through ADH. Antibodies elicited by GBPS-OMV conjugate vaccine also showed binding to N-propionylated GBPS conjugated to HSA. As an extension of the previous immunization schedule, four groups of monkeys were further immunized with the purified GBPS alone at week 50. There was no booster response to the pure GBPS. The sera were examined for bactericidal antibodies. Using human complement, the vaccines induced no increases in bactericidal antibody directed against group B polysaccharide determinants. However, the conjugates containing outer membrane vesicles, but not the unconjugated vesicle control vaccine induced high levels of bactericidal antibodies directed at lipopolysaccharide determinants.

不同免疫球蛋白诱导的恒河猴抗体的结合特异性 对B群脑膜炎奈瑟菌结合疫苗进行了研究 使用多种B群脑膜炎球菌多糖（GBPS）抗原 系统. 如通过ELISA测量的，抗体应答显著高于对照组。 高于含间隔基的GBPS或GBPS的N-丙酰化形式 与甲基化人血清白蛋白复合的天然GBPS相比 （HSA）。 针对所述抗体的抗体群体的特异性可以被称为特异性抗体。 间隔区，ADH，证实了他们的结合无关的肺炎球菌 9V多糖通过ADH与HSA缀合。 引发的抗体 GBPS-OMV结合疫苗也显示与N-丙酰化GBPS结合 与HSA结合。 作为上一次免疫的延伸 按照时间表，四组猴子进一步用纯化的 第50周时单独使用GBPS。 对纯GBPS没有加强反应。 检查血清中的杀菌抗体。 使用人 补体，疫苗未诱导杀菌抗体增加 针对B组多糖决定簇。 但 含有外膜囊泡的缀合物，但不含未缀合的 囊泡控制疫苗诱导高水平的杀菌抗体 针对脂多糖决定簇。