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

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。 我们在这里建议开发EC-QIV，一种基于以下的新型四价流感疫苗： 在大肠杆菌中产生的血凝素的免疫优势球形区域 表达系统（eHA 1）。生产生物活性药物的概念验证 正确折叠的eHA 1已被证明用于季节性H1N1、H3 N2和 两种B谱系流感病毒，以及几种禽流感病毒， 大流行的可能性。该技术的一个关键突破是成功地生产出 eHA 1的寡聚体形式。eHA 1寡聚体保留受体结合活性 和亲本HA分子的抗原性。eHA 1的生产率为 远远高于许可的疫苗。大肠杆菌的低生产成本 该系统将使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eHA 1在以下方面更有效： 以应对漂移和/或转移的流感病毒的出现。eHA 1是 集中在HA的免疫显性保护区，并已被证明是 比已获许可的流感疫苗更有效地预防病毒攻击 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。第二阶段SBIR提案是 以开发高生产率的商业制造工艺为中心 这将为预防季节性和大流行病提供大量快速部署能力， 流感。

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.