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

1.摘要 疫苗不匹配和延误继续阻碍季节性流感疫苗接种工作。 我们建议开发EC-QIV，一种新型的四价流感疫苗，基于 大肠杆菌中产生的免疫优势的血凝素球状结构域 表达系统(EHA1)。生物活性物质生产的概念论证 并展示了季节性H1N1、H3N2和 两种B系流感病毒，以及几种具有 大流行的可能性。这项技术的一个关键突破是成功地生产了 低聚形式的eHA1。EHA1寡聚体保留受体结合活性 亲本HA分子的抗原性。EHA1的生产效率是 显著高于许可疫苗。大肠杆菌的低生产成本 该系统将使EC-QIV在目前饱和的流感中具有很强的竞争力 疫苗市场。较短的生产周期将使eHA1在 应对漂移和/或转移的流感病毒的出现。EHA1是 专注于HA的免疫优势保护区，已被证明是 在预防病毒挑战方面比获得许可的流感疫苗更有效 在雪貂动物模型中。这项独特的技术有可能提供 更便宜、更快、更有效的流感疫苗。这项第二阶段SBIR提案是 以开发高生产率的商业制造流程为中心 这将为预防季节性和大流行提供巨大的激增能力 流行性感冒。

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.