IMMUNOGENICITY OF PNEUMOCOCCAL CONJUGATE VACCINES

描述(改编自申请人的摘要)：两个主要问题 与目前开发临床肺炎球菌的努力有关的 多糖蛋白疫苗是：1)免疫原性的变化 结合疫苗，即使载体保持不变和2) 载波启动的不可预测的影响，包括抑制 在某些情况下出现抗多糖抗体反应。建议进行的研究 旨在阐明免疫机制导致的 不同条件下多糖-蛋白质结合免疫原性的变化 将多糖偶联到相同的载体上，并确定条件 最大限度地提高载体启动的能力，以增强保护性 对后续多糖载体免疫的抗体反应。在……里面 特异性目标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分析来证明。 小鼠抗体和T细胞反应性。在具体目标2中， 多糖对载体改性处理的影响 蛋白质的第二类MHC分子将被确定。的第二个方面 具体目标2涉及Ps特定前体频率在 诱导对多糖-蛋白质结合物的免疫应答。 在特定目标3中，不同类型的抗原提呈细胞的作用 (活化的B细胞、巨噬细胞和树突状细胞)和T细胞的模式 不同抗原提呈细胞诱导的细胞源性细胞因子 将会被分析。

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.