HUMAN IMMUNE RESPONSE TO POLYSACCHARIDE-PROTEIN CONJUGATE VACCINES

B型流感嗜血杆菌(Hib)是引起细菌的主要原因。 婴幼儿脑膜炎是败血症的主要原因，败血症 关节炎、肺炎和会厌炎。6A型肺炎球菌(Pn6A)是一种 中耳炎的主要原因和引起脑膜炎的最常见类型 肺炎。针对这两种病原体的抗囊抗体具有保护性； 它们在幼虫体内的诱导作用受到以下因素的阻碍 它们的年龄相关的免疫原性和缺乏无名氏反应。在……里面 相比之下，由这些多糖组成的结合物共价结合到 破伤风类毒素对小鼠和幼年恒河猴有免疫原性；这种反应 可能会通过进一步的注射而增加。成年志愿者接种了疫苗 用由Hib组成的结合物每隔三周两次， 大肠杆菌K100，或Pn6A多糖和破伤风类毒素。本地 反应是常见的，可能是由于预先存在的阿尔萨斯反应 破伤风抗毒素。受者中有10人在第一次治疗后出现发热。 注射；第二次注射后无一例发生。Hib-TT引发了180倍的 Hib抗体升高。Pn6A-TT引起了大约8倍的增长 Pn6A抗体。每一种结合物诱导TT增加10到20倍 抗体。大多数志愿者在第一次治疗后出现最大反应 注射，第二次注射后未观察到助推反应。 未发现免疫前水平与发病率之间的关系。 抗体升高或疫苗的副作用。相似抗体 50或100微克剂量和一种结合物或 共轭化合物的组合。免疫前和免疫后血清中均有Hib 由Ig G、Ig M和Ig A组成的抗体。免疫接种产生了 免疫球蛋白应答最高。同样，免疫前和免疫后的血清 分布在所有的免疫球蛋白亚类中，响应最高的是 IgG2。制备了Pn6A-TT和Hib-TT，免疫18个月 在瑞典哥登堡，两岁以下的儿童开始接受教育。

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.