IMMUNE RESPONSE TO GROUP B MENINGOCOCCAL CAPSULAR POLYSACCHARIDE

对 B 组脑膜炎球菌荚膜多糖的免疫反应

• 批准号: 3748105
• 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/3748105
• 关键词: Macaca mulatta; Neisseria meningitidis; Neisseria meningitidis vaccine; active immunization; antibacterial antibody; antibody specificity; bacterial capsules; bacterial polysaccharides; bactericidal immunity; chemical structure function; immunoconjugates; immunomodulators

Alpha (2->8) polysialic acid (PSA) forms the capsular polysaccharide (CPS) of group B Neisseria meningitidis(GBNM), Escherichia coli K1 (ECK1) and a part of E. coli K92 CPS. PSA is a poorly immunogenic, T- independent, conformationally complex and is associated with pathogenesis and protection in GBNM and ECK1 infections. Its poor immunogenicity is attributed mainly to the presence of PSA in fetal mammalian tissues. Recently, PSA has been rendered immunogenic by covalent coupling with various protein carriers. However, these conjugates hve not been administered into humans, because of concern for possible autoimmune consequences. We therefore evaluated the immunogenicity of 7 different group B meningococcal polysaccharide (GBPS) vaccines in juvenile rhesus monkeys. GBPS non-covalently complexed with OMV (Dr. W. Zollinger), GBPS covalently conjugated to CRM-197 (Dr. R. Rappouli) and to OMP (LBP, DBP), N-propionylated GBPS conjugated to OMP3 (Dr. J. Tai), and K92-TT (LBP, DBP) were used in saline, aluminum hydroxide, stearyl tyrosine or MPL+TDM adjuvants. One year old rhesus were immunized i.m. three times at weeks 0, 6 and 14 and bled at various post-immunization periods.There was variation in antibody responses among individual monkeys. All vaccines except K92-TT elicited a two-fold or greater increase in GBPS antibodies after the first immunization. All vaccines including the K92-TT elicited a rise in GBPS antibodies after the first immunization. All vaccines including the K92-TT elicited a rise in GBPS antibody level of five-fold or more after the third immunization. Most of the antibodies elicited by N-propionylated GBPS-OMP3 vaccines were directed to the N- propionylated GVPS-HSA antigen rather than to native GBPS. The K92-TT conjugate also elicited antibodies to group C meningococcal polysaccharide. High levels of anti-OMP antibodies were elicited by the GBPS-OMP conjugates.Antibodies elicited by GBPS-OMP conjugate administered with and without MPL+TDM were most bactericidal in presence of human and rabbit complements. The vaccine-induced antibodies did not seem to cause any visible safety-related symptoms in the animals.

α（2->8）聚唾液酸（PSA）形成荚膜多糖 (CPS)B群脑膜炎奈瑟菌（GBNM）、大肠埃希菌K1 （ECK 1）和E. coli K92 CPS. PSA是一种免疫原性差的T- 独立的，构象复杂的，并与发病机制 以及对GBNM和ECK 1感染的保护。 其免疫原性差， 这主要归因于PSA在胎儿哺乳动物组织中的存在。 最近，PSA通过共价偶联具有免疫原性， 各种蛋白质载体。 然而，这些缀合物还没有被发现。 由于担心可能的自身免疫性， 后果 因此，我们评估了7种不同的免疫原性。 B群脑膜炎球菌多糖（GBPS）疫苗在幼年恒河猴中的应用 猴子 与OMV非共价复合的GBPS（W. Zollinger），GBPS 与CRM-197共价缀合（R. Rappouli）和OMP（LBP，DBP）， 与OMP 3缀合的N-丙酰化GBPS（Dr. J. Tai）和K92-TT（LBP， DBP）分别用于生理盐水、氢氧化铝、硬脂酰酪氨酸或MPL+TDM 佐剂 1岁恒河猴肌肉注射免疫。每周三次 0、6和14，并在不同的免疫后时期流血的。 个体猴子之间抗体反应的差异。 所有疫苗 除了K92-TT引起GBPS抗体增加2倍或更多之外， 第一次免疫后。 所有疫苗，包括K92-TT， 第一次免疫后GBPS抗体升高。 所有疫苗 包括K92-TT在内的抗GPPS抗体水平升高了5倍， 或在第三次免疫后。 大多数抗体 通过N-丙酰化的GBPS-OMP 3疫苗， 丙酰化GVPS-HSA抗原而不是天然GBPS。 K92-TT 偶联物也能诱发抗C群脑膜炎球菌抗体 多糖 高水平的抗-OMP抗体被诱导， GBPS-OMP偶联物. GBPS-OMP偶联物引发的抗体 在存在的情况下，联合和不联合MPL+TDM给药的杀菌作用最强。 人类和兔子的互补物 疫苗诱导的抗体没有 似乎会在动物中引起任何可见的安全性相关症状。