Recombinant Protein Immunogens

重组蛋白免疫原

• 批准号: 8327071
• 负责人: Shiu-Lok Hu
• 金额: $ 33.65万
• 依托单位: DANA-FARBER CANCER INST
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-05 至 2013-08-16
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8327071
• 关键词: Active Immunization; Adenoviruses; Adjuvant; Antigen Presentation Pathway; Antigens; Cellular Immunity; Escherichia coli; Gagging; Glycoproteins; Goals; HIV; HIV Antigens; HIV-1; Immune response; Immunization; Monoclonal Antibodies; Production; Protein Subunits; Proteins; Reagent; Recombinant Proteins; Recombinants; Research Personnel; SIV envelope glycoprotein gp160; Vaccination; Vaccinia virus; Viral Vector; antibody-dependent cell cytotoxicity; env Genes; gp160; mutant; nef Protein; neutralizing antibody; particle; programs; response; transmission process; vector

Bi-modal (also known as "prime-boost") immunization takes advantage of the diverse responses generated by immunogens presented in different contexts. These include innate responses to different adjuvants and vectors, as well as antigen-specific responses resulting from different antigen presentation pathways. In recent years, effort has been focused on generating cell-mediated immunity (CMI) by the use of non-replicating viral vectors, such as MVA or replication-defective adenovirus, and DMAvaccines. However, the importance of humoral responses, including broadly reactive neutralizing antibodies and antibody- dependent cellular cytotoxicity (ADCC) activities, has been increasingly recognized. Therefore, it is necessary to explore prime-boost strategies likely to induce both CMI and humoral responses. An attractive strategy is exemplified by priming with replication-competent viral vectors (e.g., adenovirus) expressing multiple HIV antigens, followed by boosting with subunit protein immunogens, as proposed in this Program Project. The overall goal of this Core is to provide investigators in Projects 2 and 3 with recombinant subunit proteins, including HIV-1 clade C gp160, SIV Gag-Pol particles, as well as recombinant SIVmac239 Nef protein. The specific aims of this Core are: (1) To express, characterize and purify clade C HIV-1 envelope glycoprotein gp160 from recombinant vaccinia viruses; (2) To express, characterize and purify SIVmac239 Gag-Pol particles from recombinant vaccinia viruses; (3) To express, characterize and purify SIVmac239 Nef from recombinant E. coli.

双模式（也称为“初免-加强”）免疫利用了不同的反应 由不同环境中存在的免疫原产生。这些包括对不同的本能反应 佐剂和载体，以及不同抗原呈递产生的抗原特异性反应 途径。近年来，人们的努力集中在通过使用细胞介导的免疫（CMI）来产生细胞介导的免疫（CMI）。 非复制病毒载体，例如 MVA 或复制缺陷型腺病毒，以及 DMA 疫苗。然而， 体液反应的重要性，包括广泛反应性中和抗体和抗体 依赖细胞的细胞毒性（ADCC）活性，已得到越来越多的认识。因此，它是 有必要探索可能诱导 CMI 和体液反应的初免-加强策略。一个有吸引力的 该策略的例子是用具有复制能力的病毒载体（例如腺病毒）表达 多种 HIV 抗原，然后按照本计划中的建议使用亚基蛋白免疫原进行加强 项目。 该核心的总体目标是为项目 2 和 3 的研究人员提供重组亚基 蛋白质，包括 HIV-1 clade C gp160、SIV Gag-Pol 颗粒以及重组 SIVmac239 Nef 蛋白质。该核心的具体目标是： (1) 从重组体中表达、表征和纯化 C 分支 HIV-1 包膜糖蛋白 gp160 痘苗病毒； (2) 表达、表征和纯化来自重组痘苗病毒的SIVmac239 Gag-Pol颗粒； (3) 从重组大肠杆菌中表达、表征和纯化 SIVmac239 Nef。