IMMUNOGENICITY OF PNEUMOCOCCAL CONJUGATE VACCINES

描述（改编自申请人摘要）：两个主要问题 关于目前努力发展临床肺炎球菌 多糖-蛋白疫苗的免疫原性的变化是：1）多糖-蛋白疫苗的免疫原性的变化 偶联疫苗，即使当载体保持相同时，和2）偶联疫苗的载体保持不变。 载体引发的不可预测的影响，包括抑制 抗多糖抗体反应在某些情况下。 拟议的研究 旨在阐明免疫学机制， 当多糖-蛋白质缀合物的免疫原性不同时， 将多糖偶联到同一载体上， 最大限度地提高载体启动的能力， 抗体对随后的多糖载体免疫的应答。 在 具体目标1，三种肺炎球菌免疫原性的差异 多糖-蛋白质结合物将通过血清 抗体和T细胞反应性。 具体目标2 多糖对载体改性的影响 将确定II类MHC分子对蛋白质的影响。 的第二方面 具体目标2涉及Ps特异性前体频率在 诱导对多糖-蛋白质缀合物的免疫应答。 在特异性目的3中，不同类型的抗原呈递细胞的作用 （活化的B细胞、巨噬细胞和树突状细胞）和T细胞的模式 由不同抗原呈递细胞引起的细胞源性细胞因子 将进行分析。

DESCRIPTION (Adapted from applicant's abstract): Two major problems pertaining to current efforts to develop clinical pneumococcal polysaccharide-protein vaccines are: 1) variation in the immunogenicity of conjugate vaccines even when the carrier remains the same and 2) the unpredictable effects of carrier priming including suppression of the anti-polysaccharide antibody response in some cases. The proposed studies are designed to elucidate the immunologic mechanisms responsible for variation in polysaccharide-protein conjugate immunogenicity when different polysaccharides are coupled to the same carrier and to determine conditions that maximize the ability of carrier priming to boost the protective antibody response to subsequent polysaccharide-carrier immunizations. In Specific Aim 1, variations in immunogenicity of three pneumococcal polysaccharide-protein conjugates will be documented by assays of serum antibody and T cell responsiveness in mice. In Specific Aim 2, the influence of the polysaccharide in altering processing of the carrier protein by class II MHC molecules will be determined. A second aspect of Specific Aim 2 involves the role of Ps-specific precursor frequency in the induction of the immune response to the polysaccharide-protein conjugate. In Specific Aim 3, the roles of different types of antigen presenting cells (activated B cells, macrophages, and dendritic cells) and the patterns of T cell-derived cytokines elicited by the different antigen-presenting cells will be analyzed.