Production of an NP-ISS conjugate vaccine to combat pandemic influenza.

生产 NP-ISS 结合疫苗以对抗大流行性流感。

• 批准号: 7478089
• 负责人: Gary A Van Nest
• 金额: $ 161.67万
• 依托单位: DYNAVAX TECHNOLOGIES CORPORATION
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-08-15 至 2009-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7478089
• 关键词: Animal Model; Birds; Cellular Immunity; Combined Vaccines; Conjugate Vaccines; Development; Dose; Drug Formulations; Elderly; Escherichia coli; Ferrets; Goals; Guanosine Monophosphate; Immunity; Immunization; Inactivated Vaccines; Influenza; Link; Modeling; Mus; Nucleoproteins; Oligonucleotides; Primates; Process; Production; Recombinants; Standards of Weights and Measures; System; Toxicology; Vaccines; immunogenicity; influenzavirus; novel vaccines; pandemic influenza; scale up

DESCRIPTION (provided by applicant): The goal of this proposal is to continue the product development of a novel vaccine approach that incorporates nucleoprotein (NP) as a conserved internal component of influenza virus linked to an immunostimulatory oligonucleotide to induce protective immunity against divergent and potentially pandemic influenza strains. Specifically, the plan is to complete process development and scale up for GMP production of recombinant NP in an E. coli system. Process development, scale-up and GMP production of the NP-ISS conjugate for the vaccine will then be performed, as well as IND enabling toxicology and stability studies. In addition, characterization of the immunogenicity and protective immunity provided by the NP-ISS vaccine alone and NP-ISS combined with standard trivalent inactivated vaccine will be performed in animal models. The Specific Aims of the proposal are: 1. Produce GMP-grade NP-ISS conjugate * GMP manufacture of recombinant nucleoprotein in the E. coli production system * Process development and scale-up of NP-ISS conjugate formulation * GMP manufacture of NP-ISS formulation 2. Perform IND enabling toxicology on NP-ISS vaccine ¿ TIV 3. Perform further characterization of the NP-ISS vaccine. * Assess protection provided by E. coli derived NP-ISS in the mouse challenge model against drift (H1), shift (H3) and avian (H5) influenza strains. * Assess protection following immunization in the ferret influenza challenge model with drift (H1),shift (H3) and avian (H5) influenza strains. * Optimize the combination of NP-ISS and TIV in primates to allow HA dose sparing while inducing NP-specific cell mediated immunity. * Evaluate immunogenicity of the NP-ISS vaccine combined with trivalent inactivated vaccine in elderly mice.

描述（由申请人提供）：本申请的目标是继续开发一种新型疫苗方法，该方法将核蛋白（NP）作为流感病毒的保守内部成分，与免疫刺激寡核苷酸连接，以诱导针对不同和潜在大流行性流感毒株的保护性免疫。具体来说，该计划是在大肠杆菌系统中完成重组NP的GMP生产的工艺开发和规模扩大。然后将进行疫苗的NP-ISS偶联物的工艺开发、扩大规模和GMP生产，以及IND支持的毒理学和稳定性研究。此外，将在动物模型中对NP-ISS疫苗单独和NP-ISS与标准三价灭活疫苗联合提供的免疫原性和保护性免疫进行表征。建议的具体目标是：