HUMAN T CELL RESPONSE TO PNEUMOCOCCAL CONJUGATE VACCINES

针对肺炎球菌荚膜多糖（PnPs）的各种致病性血清型的抗体提供免受感染的保护，但纯PnPs是T细胞非依赖性抗原，并且在儿童和老年人中是差的免疫原。PnPs与载体蛋白的缀合改善PnPs特异性抗体（Ab）应答和eliminant T细胞帮助。实验性肺炎球菌-蛋白质缀合物疫苗使用纯化的PnPs特异性B细胞前体，或者其是否是由于PnPs特异性B细胞前体的血清型的影响，或者其是否是由于PnPs的血清型对CRM 197的抗原加工的影响，从而在随后的人类T细胞辅助中产生改变。我们将用实验性7价PnP-CRM/197疫苗免疫50名成年志愿者，并测量针对每种血清型以及CRM/197的Ab水平。我们还将确定对某些CRM/197表位特异性的供体外周CD 4 + T细胞是否与PnPs的更好免疫原性相关。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区基因使用对于低应答血清型是否不同。最后，我们将研究PnPs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。这些数据将大大增加我们对结合疫苗免疫应答的理解，并可能为第二代疫苗的设计提供有用的信息。

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.