公开(公告)号：US5445817A

公开(公告)日：1995-08-29

申请号：US932960

申请日：1992-08-21

申请人： Rachel Schneerson ,  Lily Levi ,  John B. Robbins

发明人： Rachel Schneerson ,  Lily Levi ,  John B. Robbins

IPC分类号： A61K39/116 ,  A61K47/48 ,  A61K39/385 ,  A61K39/09 ,  A61K39/10

CPC分类号： A61K47/4833 ,  A61K39/092 ,  A61K2039/6037 ,  Y10S424/831

摘要： A medically important and useful conjugate comprising pertussis toxin (PT), or another antigen having similar physico-chemical properties, as the carrier protein component, coupled to a neutral or non-charged saccharide, particularly, the capsular polysaccharide of Streptococcus pneumoniae type 14 (Pn14), for use as an effective, non-toxic, and highly immunogenic vaccine is described. The invention is directed to a novel synthetic scheme wherein PT and like proteins, and a derivative of Pn14, and the like, were coupled at acidic pH via carbodiimide-mediated condensation to produce an immunogenic conjugate. The coupling procedure yielded a Pn14-PT conjugate in which the PT component was rendered non-toxic and both the PT and Pn14 components were immunogenic, as determined by the production of protective levels of both type-specific and neutralizing antibodies in mammals. The Pn14-PT conjugate was used as an immunogen at levels estimated to be protective in humans and stands to provide an effective, safe, and potent human vaccine.

摘要翻译： 包含百日咳毒素（PT）或具有相似物理化学性质的另一抗原作为载体蛋白组分的医学上重要且有用的缀合物偶联到中性或非带电糖，特别是14型肺炎链球菌的荚膜多糖（ Pn14）用作有效，无毒，高免疫原性疫苗。 本发明涉及一种新颖的合成方案，其中PT等蛋白质和Pn14衍生物等通过碳二亚胺介导的缩合在酸性pH下偶联以产生免疫原性缀合物。 偶联方法产生Pn14-PT缀合物，其中PT组分无毒，并且PT和Pn14组分都是免疫原性的，如通过哺乳动物中特异性和中和抗体的保护水平的产生所确定的。 Pn14-PT缀合物用作免疫原，其水平估计在人体中是保护性的，并且提供有效，安全和有效的人类疫苗。