HUMAN IMMUNE RESPONSE TO POLYSACCHARIDE-PROTEIN CONJUGATE VACCINES

多糖蛋白结合疫苗的人体免疫反应

• 批准号: 2575681
• 负责人: R SCHNEERSON
• 金额: --
• 依托单位: EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT
• 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/2575681
• 关键词: Shigella vaccines; Streptococcus vaccine; active immunization; bacterial polysaccharides; bactericidal immunity; chronic renal failure; clinical research; clinical trial phase I; drug screening /evaluation; human subject; immunoconjugates; immunoglobulins; infant human (0-1 year); laboratory mouse; sickle cell anemia; tetanus toxoid

The surface polysaccharides of bacterial pathogens including capsular polysaccharides and lipopolysaccharides serve as protective antigens. The immunologic properties of these bacterial polysaccharides namely their age-related and T-cell independent immunogenicity limit their use as vaccines. Covalently attachment to medically-useful proteins to form conjugates. both increases their immunogenicity and confers T-cell dependent properties to these polysaccharides. The capsular polysaccharides of Streptococcus pneumococcus type 6B have been bound to tetanus toxoid and evaluated clinically. S. aureus type 5-rEPA was evaluated in end stage renal disease patients; type 5 antibodies of the three major Ig classes rose significantly though to a lesser degree compared to healthy volunteers. As expected, there was no booster response to reinjection. These vaccine-induced antibodies had opsonophagocytic activities. Pn6B-TT was evaluated in patients with sickle cell disease, healthy infants at 3, 4 and 6 months of age or at 7 and 9 months of age. Type specific antibodies of the three Ig classes, with booster responses, were induced. The magnitude of these responses was lesser than of Hib-TT. All conjugates were safe, with only minor local reaction. The LPS of shigellae was detoxified, their 0-specific polysaccharides bound to bacterial toxoids and their immunogenicity in mice found to be satisfactory. In Phase 1 and Phase 2 studies, these conjugates of the 0-specific polysaccharides were safe and immunogenic: LPS antibody levels elicited by the investigational conjugates were similar to those in recruits convalescent from shigellosis vaccine- induced IgG persisted at high levels for two years. In preliminary though statistically significant studies, a S. sonnei-rEPA conjugate protected against shigellosis caused by this pathogen. A phase 2 study of S. sonnei and S. flexneri in children showed both conjugates to be highly safe and immunogenic. Phase 3 trials are being planned.

细菌病原体的表面多糖包括荚膜多糖 多糖和脂多糖用作保护性抗原。 这些细菌多糖的免疫学特性，即 它们的年龄相关的和不依赖于T细胞的免疫原性限制了它们的应用 as vaccines疫苗.粘附在医学上有用的蛋白质上， 结合物。都增加了它们的免疫原性，并赋予T细胞 依赖于这些多糖的性质。囊 肺炎链球菌6 B型的多糖已经结合到 破伤风类毒素和临床评价。 S.金黄色葡萄球菌5型-rEPA是 在终末期肾病患者中进行评估; 三个主要的IG类显著上升，尽管程度较小 与健康志愿者相比。 不出所料，没有助推器 回复回复回复 这些疫苗诱导的抗体 调理吞噬活性。Pn 6 B-TT在患有以下疾病的患者中进行了评价： 镰状细胞病，3、4和6个月大的健康婴儿或 7和9个月大。 三种IG类的型特异性抗体， 与加强反应，被诱导。 这些反应的强度 低于Hib-TT。 所有结合物都是安全的， 当地反应。 志贺氏菌的LPS被解毒，它们的0-特异性 与细菌类毒素结合的多糖及其免疫原性 小鼠被认为是令人满意的。 在1期和2期研究中，这些 0-特异性多糖的缀合物是安全的和免疫原性的： 由研究性缀合物引发的LPS抗体水平为 与接种志贺氏菌病疫苗后恢复期的新兵相似， 诱导的IgG持续高水平两年。 初步 尽管有统计学意义的研究，一个S。Sonnei-rEPA结合物 防止由这种病原体引起的志贺氏菌病。 一项2期研究 色葡萄sonnei和S.在儿童的flexneri表明，这两种共轭物是 高度安全且具有免疫原性。 3期试验正在计划中。