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: 3965839
• 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/3965839
• 关键词: Escherichia coli; Haemophilus influenzae; Haemophilus influenzae vaccines; Scandinavian country; Streptococcus pneumoniae; Streptococcus pneumoniae vaccine; antibacterial antibody; bacterial antigens; bacterial capsules; bacterial meningitis; bacterial pneumonia; bacterial polysaccharides; bactericidal immunity; child (0-11); enzyme linked immunosorbent assay; epiglottis; human subject; immunization; immunoconjugates; immunological substance; otitis media; radioimmunoassay; tetanus toxoid

Haemophilus influenzae type b (Hib) is the leading cause of bacterial meningitis in infants and children and a major cause of septicemia, septic arthritis pneumonia and epiglottitis. Pneumococcus type 6A (Pn6A) is a major cause of otitis media and the most frequent type causing meningitis pneumonia. Anticapsular antibodies to these two pathogens are protective; their induction in the young by capsular polysaccharides is hampered by both their age-related immunogenicity and lack of anamestic response. In contrast, conjugates composed of these polysaccharides covalently bound to tetanus toxoid were immunogenic in mice and infant rhesus; this response could be boosted by further injections. Adult volunteers were immunized two times at three week intervals with conjugates composed of Hib, Escherichia coli K100, or Pn6A polysaccharides and tetanus toxoid. Local reactions were common and probably due to Arthus reaction by preexisting tetanus antitoxin. Fever occurred in ten of the recipients after the first injection; in none after the second injection. Hib-TT elicited a 180-fold increase in Hib antibody. Pn6A-TT elicited about an 8-fold increase in Pn6A antibody. Each conjugate induced a 10 to 20-fold increase in TT antibodies. A maximal response occurred in most volunteers after the first injection, with no booster response observed after the second injection. No relation was found between the preimmune levels with the rate of antibody rise or to the side effects of the vaccines. Similar antibody levels were induced by 50 or 100 ug doses and by one conjugate or combination of conjugates. Pre and post-immunization sera had Hib antibodies composed of IgG, IgM, and IgA. Immunization produced the highest response in IgG. Similarly, pre and post-immunization sera were distributed among all IgG subclasses, with the highest response in the IgG2. Pn6A-TT and Hib-TT have been prepared and immunization of 18 month to 2 year old children has begun in Gotenborg, Sweden.

流感嗜血杆菌B型（HiB）是引起细菌性肺炎的主要原因。 婴儿和儿童的脑膜炎和败血症的主要原因， 关节炎、肺炎和会厌炎。 肺炎球菌6A型（Pn 6A）是一种 中耳炎的主要原因和最常见的类型引起脑膜炎 肺炎 针对这两种病原体的抗囊抗体具有保护作用; 它们在幼鼠中被荚膜多糖诱导， 它们与年龄相关的免疫原性和缺乏记忆应答。 在 相反，由这些多糖共价结合到 破伤风类毒素在小鼠和幼年恒河猴中具有免疫原性;这种反应 可以通过进一步注射来增强。 成年志愿者接种疫苗 每隔三周用由Hib组成的缀合物进行两次， 大肠杆菌K100或Pn 6A多糖和破伤风类毒素。 当地 反应常见，可能是由于先前存在的Arthus反应 破伤风抗毒素 在第一次注射后， 注射;第二次注射后无。 Hib-TT引起了180倍的 Hib抗体增加。 Pn 6A-TT引起了约8倍的增加， Pn 6A抗体。 每种缀合物诱导TT增加10至20倍， 抗体的 大多数志愿者在第一次注射后出现最大反应， 注射，在第二次注射后没有观察到加强反应。 未发现免疫前水平与 抗体上升或疫苗的副作用。 类似抗体 50或100 μ g剂量和一种缀合物或 缀合物的组合。 免疫前和免疫后血清中均有Hib 由IgG、IgM和伊加组成的抗体。 免疫接种产生了 IgG的最高反应。 类似地，免疫前和免疫后的血清被 分布在所有IgG亚类中，其中在 IgG 2。 已制备Pn 6A-TT和Hib-TT并免疫18个月 在瑞典的哥德堡开始了对2岁儿童的教育。