Development of a novel quadrivalent seasonal influenza vaccine using E.coli production technology

利用大肠杆菌生产技术开发新型四价季节性流感疫苗

• 批准号: 9201957
• 负责人: SHENGQIANG LI
• 金额: $ 73.75万
• 依托单位: SCIOGEN, LLC
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-08-01 至 2018-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9201957
• 关键词: Address; Affinity Chromatography; Animal Model; Antibodies; Antibody Affinity; Antibody Response; Avian Influenza A Virus; Baculoviruses; Binding; Biological Assay; California; Cell Culture Techniques; Chromatography; Clinical; Collaborations; Development; Electron Microscopy; Escherichia coli; Evaluation; Ferrets; Goals; Hemagglutination; Hemagglutinin; Human; Hydrophobic Interactions; Immune response; Immunodiffusion; Influenza; Influenza A Virus, H1N1 Subtype; Influenza vaccination; Ion-Exchange Chromatography Procedure; Lead; Licensing; Marketing; Measures; Modeling; Molecular Sieve Chromatography; Nasal Lavage Fluid; Negative Staining; Phase; Prevention; Process; Production; Productivity; Property; Radio; Recombinant Vaccines; Risk; Seasons; Small Business Innovation Research Grant; Surface Plasmon Resonance; Switzerland; Symptoms; System; Technology; TimeLine; Vaccinated; Vaccine Production; Vaccines; Viral Load result; Virus; abstracting; analytical tool; base; biophysical properties; cost; egg; immunogenic; improved; influenza virus vaccine; influenzavirus; manufacturing process; monomer; neutralizing antibody; novel; pandemic disease; pandemic influenza; receptor; receptor binding; scale up; seasonal influenza; vaccine development; vaccine efficacy

1. Abstract Vaccine mismatch and delay continue to hamper seasonal influenza vaccination efforts. We propose here to develop EC-QIV, a novel quadrivalent influenza vaccine based on the immunologically dominant globular domain of hemagglutinin produced in an E.coli expression system (eHA1). The proof of concept for production of biologically active and correctly folded eHA1 has been demonstrated for the seasonal H1N1, H3N2, and two B lineage influenza viruses, as well as for several avian influenza viruses with pandemic potential. A key breakthrough of this technology is the successful production of the oligomeric form of eHA1. The eHA1 oligomer retains the receptor binding activity and the antigenicity of the parental HA molecule. The productivity of eHA1 is significantly higher than that of licensed vaccines. The low production cost of the E.coli system will allow EC-QIV to be highly competitive in the current saturated influenza vaccine market. A short production cycle will allow eHA1 to be more efficient in responding to emergence of drifted and or shifted influenza viruses. The eHA1 is focused on the immunodominant protective region of HA and has been shown to be more effective than the licensed influenza vaccines in protection against virus challenge in the ferret animal model. This unique technology has the potential to provide cheaper, faster, and more effective influenza vaccines. This Phase II SBIR proposal is centered on the development of a highly productive commercial manufacturing process that will provide significant surge capacity for prevention of seasonal and pandemic influenza.

1. 摘要 疫苗不匹配和延迟继续阻碍季节性流感疫苗接种工作。 我们在此建议开发EC-QIV，一种基于 大肠杆菌产生的血凝素的免疫优势球状结构域 表达系统（eHA1）。生产生物活性物质的概念验证 正确折叠的 eHA1 已被证明可用于季节性 H1N1、H3N2 和 两种 B 系流感病毒，以及几种带有 大流行可能性。该技术的关键突破在于成功量产 eHA1 的寡聚形式。 eHA1寡聚体保留了受体结合活性 以及亲代HA分子的抗原性。 eHA1 的生产率为 明显高于许可疫苗。大肠杆菌的生产成本低 系统将使EC-QIV在当前饱和的流感中具有高度竞争力 疫苗市场。较短的生产周期将使 eHA1 更加高效 对漂移和/或转移的流感病毒的出现做出反应。 eHA1 是 专注于 HA 的免疫显性保护区域，并已被证明 在预防病毒攻击方面比获得许可的流感疫苗更有效 在雪貂动物模型中。这种独特的技术有潜力提供 更便宜、更快、更有效的流感疫苗。第二阶段 SBIR 提案是 以开发高生产力的商业制造工艺为中心 这将为预防季节性和流行病提供巨大的增援能力 流感。