IMMUNE RESPONSE TO GROUP B MENINGOCOCCAL CAPSULAR POLYSACCHARIDE

α(2-gt；8)聚唾液酸(PSA)形成胶囊多糖 B群脑膜炎奈瑟菌(GBNM)，大肠杆菌K1 (ECK1)和部分E.ColiK92CPS。PSA是一种免疫原性很差的T- 独立的，构象复杂的，与发病有关 以及对GBNM和ECK1感染的保护。它的免疫原性很差 主要归因于胎儿哺乳动物组织中PSA的存在。 最近，PSA通过与PSA的共价偶联被认为是免疫原性的 各种蛋白质载体。然而，这些共轭词还没有 注射给人类，因为担心可能的自身免疫 后果。因此，我们评估了7种不同的免疫原性 幼年恒河猴接种B群脑膜炎球菌多糖疫苗 猴子。与OMV非共价络合(W.Zollinger博士) 共价连接到CRM-197(R.Rappouli博士)和OMP(LBP，DBP)， 偶联到OMP3的N-丙酰化GBP(J.戴博士)和K92-TT(LBP， DBP)用于生理盐水、氢氧化铝、硬脂酰酪氨酸或MPL+TDM 佐剂。对1岁恒河猴进行免疫接种。每周三次 0，6和14，并在不同的免疫后时期出血。 猴子个体间抗体反应的差异。所有疫苗 除了K92-TT诱导的GBP抗体增加了一倍或更多 在第一次免疫后。包括K92-TT在内的所有疫苗都被引出 第一次免疫后GBP抗体升高。所有疫苗 包括K92-TT在内，Gbps抗体水平上升了五倍 或在第三次免疫后更多。大多数抗体都会引起 通过N-丙酰化GBP-OMP3疫苗针对N- 丙酰化的GVPS-HSA抗原，而不是天然的GBP。K92-TT 结合物还可诱导C群脑膜炎双球菌抗体 多糖类。高水平的抗OMP抗体是由 Gbps-OMP结合物.Gbps-OMP结合物诱导的抗体 在有无MPL+TDM存在的情况下，给药后杀菌效果最好 人类和兔子的互补。疫苗诱导的抗体没有 似乎会在动物身上引起任何明显的安全相关症状。

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.