HUMAN T CELL RESPONSE TO PNEUMOCOCCAL CONJUGATE VACCINES

人类 T 细胞对肺炎球菌结合疫苗的反应

• 批准号: 6511181
• 负责人: JOHN R SCHREIBER
• 金额: $ 30.2万
• 依托单位: CASE WESTERN RESERVE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-07-01 至 2005-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6511181
• 关键词: B lymphocyte; Streptococcus pneumoniae; Streptococcus pneumoniae vaccine; T lymphocyte; active immunization; antibody formation; clinical research; genetic strain; human subject; laboratory mouse; leukocyte activation /transformation; microorganism immunology

Antibodies against the various pathogenic serotypes of pneumococcal capsular polysacharides (PnPs) provide protection from infection , but pure PnPs are T cell independent antigens and are poor immunogens in children and elderly. Conjugation of PnPs to a carrier protein improves the PnPs-specific antibody (Ab) response and elicits T cell help. The experimental pneumococcal-protein conjugate vaccine uses purified PnPs-specific B cell precursors or whether it is due to the effect of the serotype of the PnPs-specific B cell precursors or whether it is due to the effect of the serotype off the PnPs on the antigen processing of CRM197 yielding alterations in subsequent T cell help in humans. We will immunize fifty adult volunteers with the experimental 7 valent PnPs- CRM/197 vaccine and measure Ab levels against each serotype as well as CRM/197. We will also determine if donor peripheral CD4+ T cells specific for certain CRM/197 epitopes are associated with better immunogenicity of PnPs. Next, we will examine the frequency of PnPs- specific B cell precursors in each donor and determine if PnPs-specific B cell frequency correlates with PnPs Ab titer. We will also determine if PnPs antibody V region gene usage is different for low responder serotypes. Finally, we will examine whether the serotype of PnPs affects processing and presentation of carrier protein-derived epitopes by human antigen processing cells, yielding differences in subsequent T cell help. These data will significantly add to our understanding of the immune response to conjugate vaccines and may provide information useful to the design of second-generation vaccines.

针对肺炎球菌荚膜多糖 (PnP) 的各种致病性血清型的抗体可提供免受感染的保护，但纯 PnP 是 T 细胞独立抗原，对于儿童和老年人来说是较差的免疫原。 PnP 与载体蛋白的缀合可改善 PnP 特异性抗体 (Ab) 反应并引发 T 细胞帮助。实验性肺炎球菌蛋白结合疫苗使用纯化的 PnPs 特异性 B 细胞前体，或者是否是由于 PnPs 特异性 B 细胞前体的血清型的影响，或者是否是由于 PnP 的血清型对 CRM197 抗原加工的影响，从而在随后的人类 T 细胞帮助中产生改变。我们将使用实验性 7 价 PnPs-CRM/197 疫苗对 50 名成年志愿者进行免疫，并测量每种血清型以及 CRM/197 的抗体水平。我们还将确定对某些 CRM/197 表位具有特异性的供体外周 CD4+ T 细胞是否与 PnP 更好的免疫原性相关。接下来，我们将检查每个供体中 PnPs 特异性 B 细胞前体的频率，并确定 PnPs 特异性 B 细胞频率是否与 PnPs Ab 滴度相关。我们还将确定 PnPs 抗体 V 区基因的使用对于低反应者血清型是否有所不同。最后，我们将检查 PnP 的血清型是否影响人类抗原加工细胞对载体蛋白衍生表位的加工和呈递，从而在随后的 T 细胞帮助中产生差异。这些数据将显着增加我们对结合疫苗免疫反应的理解，并可能为第二代疫苗的设计提供有用的信息。