A Novel Cassette System for the Assembly of VLP Vaccines

用于组装 VLP 疫苗的新型盒式系统

• 批准号: 8393900
• 负责人: Michael N Blackburn
• 金额: $ 29.67万
• 依托单位: SHIFA BIOMEDICAL CORPORATION
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-06-01 至 2014-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8393900
• 关键词: Address; Affinity; Animal Model; Animals; Antibodies; Antigens; Bacteria; Bacterial Infections; Bacteriophages; Binding; Capsid; Capsid Proteins; Cause of Death; Cells; Cervarix; Cessation of life; Chimeric Proteins; Communicable Diseases; Complex; Coupled; Cysteine; Development; Disease; Disease Outbreaks; Engineering; Enterobacteria phage MS2; Escherichia coli; Goals; Hemagglutinin; Human Papilloma Virus Vaccine; Immune response; Immunologic Techniques; Individual; Industry; Infection prevention; Influenza; Influenza A Virus, H1N1 Subtype; Influenza Hemagglutinin; Insecta; Link; Linker DNA; Literature; Mammalian Cell; Methods; Methyl Green; Mus; Oranges; Phase; Procedures; Production; Proteins; Publishing; Reagent; Recombinant Proteins; Recombinants; Structural Protein; Structure; Subunit Vaccines; System; Techniques; Technology; Testing; Time; TimeLine; Vaccination; Vaccine Production; Vaccines; Validation; Viral Antigens; Virion; Virus; Virus Diseases; Virus-like particle; Work; Zinc Fingers; aptamer; base; cost; cost effective; crosslink; design; design and construction; efficacy evaluation; immunogenicity; influenzavirus; new technology; novel; novel strategies; novel vaccines; pandemic disease; particle; plant fungi; prevent; protein folding; prototype; tool; vaccine candidate

DESCRIPTION (provided by applicant): Influenza and other infectious diseases are a major cause of death in the US and world-wide. Vaccination is the most cost-effective strategy to prevent these diseases. Although much progress has been made in vaccine technology, the timely design, validation and production of vaccines remains a major hurdle for the vaccine industry. The development of recombinant methods for the expression of subunit vaccines has impacted development timelines and costs but subunit vaccines frequently are not as potent as virus particles in eliciting an immune response. Virus like particles or VLPs represent one approach to bridge this potency gap but the design, expression and purification of VLPs remains problematic and the development of uniform tools to aid in vaccine production is elusive with existing technologies. In this proposal we describe a novel cassette technology of integrating recombinant proteins into the structure of VLPs. The prototype system defined in this proposal will generate VLPs using the influenza hemagglutinin as an immunogen. The potency of the VLP vaccine will be tested in animals in comparison to a monomeric hemagglutinin. PUBLIC HEALTH RELEVANCE: The influenza virus is highly infectious and causes both seasonal and pandemic outbreaks. A pandemic outbreak of a highly lethal strain would cause millions of deaths worldwide. Vaccines are the most cost- effective strategy to prevent infection. New strategies are required to produce more effective vaccines and to expedite the development time for new vaccines. Our goal is to develop a novel technology for the design and development of virus like particles that can be used in vaccines.

描述(申请人提供)：流感和其他传染病是美国和世界范围内的主要死亡原因。接种疫苗是预防这些疾病最具成本效益的策略。尽管疫苗技术取得了很大进展，但疫苗的及时设计、验证和生产仍然是疫苗行业的一大障碍。表达亚单位疫苗的重组方法的发展影响了开发时间表和成本，但亚单位疫苗在诱导免疫反应方面往往不如病毒颗粒那么有效。病毒样颗粒或VLP是弥合这种效力差距的一种方法，但VLP的设计、表达和纯化仍然存在问题，利用现有技术难以开发统一的工具来帮助疫苗生产。在这项建议中，我们描述了一种新的盒技术，将重组蛋白整合到VLP的结构中。该提案中定义的原型系统将使用流感血凝素作为免疫原产生VLP。VLP疫苗的效力将在动物身上进行测试，并与单体血凝素进行比较。 与公共卫生相关：流感病毒具有很高的传染性，会引起季节性和大流行疫情。一种高致命性毒株的大流行爆发将导致全球数百万人死亡。疫苗是预防感染的最具成本效益的策略。需要新的战略来生产更有效的疫苗，并加快新疫苗的开发时间。我们的目标是开发一种新技术，用于设计和开发可用于疫苗的类似病毒的颗粒。