CPG DNA ADJUVANTS AND VACCINES FOR ENCAPSULATED BACTERIA

描述：(改编自申请人摘要)：CpG寡核苷酸 (ODN)具有免疫调节作用，可能对未来的许多疫苗有用 申请。本提案目标是了解CpG ODN如何更改 抗原处理和多肽递呈给T细胞。该项目将 同时研究CpG ODN如何改变对多糖AGS、AS的体液免疫 由未结合的PS或PS-蛋白结合物免疫诱导 疫苗。 目的1：检测CpG ODN对抗原提呈细胞能力的影响 处理抗原并刺激T细胞对蛋白AGS的反应。这是假设的 CpG ODN促进树突状细胞和B细胞对抗原的加工。 研究人员将确定CpG ODN对这些细胞能力的影响 处理和提供外源蛋白AGS的细胞，包括CRM 197， AIMS 2和3中研究的糖结合疫苗的载体蛋白：机制 因为这些效应将被探索，包括CpG ODN对 MHC-II的合成和表达、肽的半衰期等因素 络合物和银加工组分的表达。 目的2：探讨CpG ODN对PS和 糖结合疫苗的多肽表位，主要使用一种实验性的 肺炎链球菌疫苗。提示CpG ODN将增强 糖结合疫苗PS表位的AB反应及抗体改变 被激发的同种类型(例如，在小鼠中诱导IgG2a和IgG3反应)。 这些影响的机制将被确定，包括 细胞因子和T细胞。 目的3：实验将测试CpG ODN是否可以作为有效的佐剂 与仅含未结合PS免疫原的疫苗协调以增强 PS特异性的IgM和IgG1反应，并诱导其他同种类型的PS特异性抗体。 这些作用的机制将被确定(例如，T细胞和 细胞因子)。 了解CpG ODN对Ag提呈细胞的调制将增加 我们对CpG ODN佐剂功能的基本机制的理解。这个 CpG ODN增强对PS AGS的体液免疫能力将使 研制针对微囊化细菌的改良疫苗。

DESCRIPTION: (Adapted from the Applicant's Abstract): CpG oligodeoxynucleotides (ODN) have immunomodulatory effects that may be useful for many future vaccine applications. The goal of this proposal is to understand how CpG ODN alter antigen processing and presentation of peptides to T cells. The project will also investigate how CpG ODN alter humoral immunity to polysaccharide Ags, as induced by immunization with either unconjugated PS or PS-protein conjugate vaccines. Aim 1: To determine the effect of CpG ODN on the ability of Ag presenting cells to process Ag and stimulate T cell responses to protein Ags. It is hypothesized that CpG ODN enhance Ag processing by dendritic cells and B cells. Investigators will determine the effects of CpG ODN on the ability of these cells to process and present exogenous protein Ags, including CRM 197, the carrier protein for glycoconjugate vaccines studied in Aims 2 and 3. Mechanisms for these effects will be explored, including the influence of CpG ODN on factors such as MHC-II synthesis and expression, half-life of peptide:MHC-II complexes, and expression of Ag processing components. Aim 2: To explore the adjuvant effects of CpG ODN on responses to PS and peptide epitopes of glycoconjugate vaccines, primarily using an experimental vaccine for Streptococcus pneumoniae. It is suggested that CpG ODN will enhance Ab responses to PS epitopes of glycoconjugate vaccines and alter the Ab isotypes that are elicited (e.g., to induce IgG2a and IgG3 responses in mice). The mechanisms of these effects will be determined including the roles of cytokines and T cells. Aim 3: Experiments will test whether CpG ODN can act as effective adjuvants in concert with vaccines containing only unconjugated PS immunogen to enhance PS-specific IgM and IgG1 responses and induce PS-specific Ab of other isotypes. Mechanisms of these effects will be determined (e.g., roles of T cells and cytokines). Understanding the modulation of Ag presenting cells by CpG ODN would increase our understanding of the basic mechanisms of adjuvant function for CpG ODN. The ability of CpG ODN to enhance humoral immunity to PS Ags would allow the development of improved vaccines for encapsulated bacteria.