PASSIVE ANTIPNEUMOCOCCAL THERAPY

被动抗肺炎球菌治疗

• 批准号: 2609981
• 负责人: Betty Diamond
• 金额: $ 30.08万
• 依托单位: ALBERT EINSTEIN COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-09-30 至 2001-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2609981
• 关键词: SCID mouse; Streptococcus pneumoniae vaccine; antibacterial antibody; bacterial antigens; bacterial polysaccharides; passive immunization; peptide library; protein sequence; synthetic vaccines; transfection /expression vector; vaccine development

DESCRIPTION: (Adapted from the applicant's abstract) Infection with Streptococcus pneumoniae remains a major cause of morbidity in the young, the elderly and those with compromised immunity. Despite antibiotics, morality from pneumococcal bacteria has never declined below 30%, and in recent years, there has been an increase in antibiotic resistant organisms among clinical isolates. An accumulation of data suggests that antibodies protect an organism from pneumococcal infection, and prior to the advent of the antibiotic era immune serum constituted an effective anti-pneumococcal therapy. For these reasons, they propose to develop immunologically based approaches to pneumococcal therapy. They propose to identify antibodies that can be used in passive therapy. They will generate these from combinatorial phage libraries derived form spleen cells of pneumovax immunized individuals. They propose to simulate somatic mutation in vitro using libraries of human anti-pneumococcal antibodies that are protective in mice against clinically significant stains to generate the most effective antibodies for the largest number of clinically important stereotypes. They will then use these antibodies to obtain peptide mimotopes which bind anti-polysaccharide antibodies and stimulate production of protective anti-pneumococcal antibodies. Finally, they will explore the use of various vectors that might be used to administer such peptide mimotopes. These include an attenuated strain of shigella and adenovirus.

描述：（改编自申请人的摘要）感染 肺炎链球菌仍然是年轻人发病的主要原因， 老年人和免疫力低下的人。 尽管使用了抗生素， 肺炎球菌造成的道德水平从未下降到 30% 以下，并且 近年来，抗生素耐药性微生物有所增加 临床分离株之间。 数据的积累表明，抗体 保护有机体免受肺炎球菌感染，并在出现之前 抗生素时代的免疫血清构成了有效的抗肺炎球菌 治疗。 由于这些原因，他们建议开发基于免疫学的 肺炎球菌治疗的方法。 他们建议鉴定可用于被动治疗的抗体。 他们将从衍生形式的组合噬菌体文库中生成这些 pneumovax 免疫个体的脾细胞。 他们建议模拟 使用人抗肺炎球菌文库进行体外体细胞突变 抗体可以保护小鼠免受临床上显着的污渍的影响 为最多数量的人产生最有效的抗体 临床上重要的刻板印象。 然后他们将使用这些抗体 获得结合抗多糖抗体的肽模拟表位并 刺激保护性抗肺炎球菌抗体的产生。 最后， 他们将探索各种载体的使用，这些载体可能用于 施用此类肽模拟表位。 其中包括减毒株 志贺氏菌和腺病毒。