Pandemic influenza DNA vaccine Development

大流行性流感DNA疫苗的开发

• 批准号: 7287998
• 负责人: LAWRENCE R SMITH
• 金额: $ 141.34万
• 依托单位: VICAL, INC.
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-06-15 至 2010-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7287998
• 关键词: Biodistribution; Biological Assay; Birds; Cessation of life; Clinical Research; Computers; Consumption; DNA; DNA Vaccines; Development; Disease Outbreaks; Dose; Drug Formulations; Evaluation; Event; Ferrets; Future; Generations; Genes; Genomics; H5 hemagglutinin; Hemagglutinin; Human; Influenza; Influenza A Virus, H5N1 Subtype; Influenza Hemagglutinin; Monitor; Mus; Numbers; Phase; Polymerase Chain Reaction; Procedures; Research; Running; Safety; Stainless Steel; Standards of Weights and Measures; System; Technology; Testing; Time; TimeLine; Toxic effect; Vaccine Production; Vaccines; Vietnam; Virus; Virus Diseases; Week; World Health Organization; base; day; design; design and construction; egg; engineering design; influenza outbreak; influenza virus vaccine; influenzavirus; milligram; novel; novel vaccines; pandemic disease; pandemic influenza; response; trivalent influenza vaccine; vaccine development

DESCRIPTION (provided by applicant): Current egg-based influenza vaccine manufacturing technology requires approximately six months to prepare sufficient doses of seasonal trivalent inactivated influenza vaccine (TIV). On several occasions in recent years, manufacturing issues have created vaccine shortages that resulted in a subsequent prioritization of vaccine recipients. Furthermore, limited surge capacity exists beyond the yearly 80-90 million doses of TIV produced for U.S. consumption, which will pose constraints on vaccine manufacture in the event of a pandemic outbreak. The current WHO Phase 3 pandemic alert status of avian to human H5N1 influenza virus infections and deaths has encouraged the development of new vaccine technologies capable of producing large numbers of doses under tightly compressed timelines. Because it is not possible to predict the exact virus strain prior to an influenza outbreak, rapid vaccine production capability is required for a timely response to an influenza pandemic. The ultimate aim of this research is to develop a manufacturing system capable of generating millions of bulk doses of hemagglutinin (HA)-based DNA vaccines within a very short time. Utilizing novel manufacturing technology already under development at Vical Incorporated, HA-based DNA vaccines would be produced against an emerging influenza strain within days to weeks after acquiring the emerging HA genomic sequence. In addition, this manufacturing system would be used during interpandemic periods to produce yearly seasonal trivalent vaccines without the constraints of the current egg-based procedures. The present aim of this proposal is to develop and characterize a polymerase chain reaction (PCR)-based manufacturing system that can rapidly produce vaccine doses comprising bulk, linear DNA expression cassettes (LECs) encoding an influenza HA gene.

描述（由申请人提供）：目前基于鸡蛋的流感疫苗制造技术需要大约六个月的时间来制备足够剂量的季节性三价灭活流感疫苗（TIV）。近年来，生产问题多次造成疫苗短缺，导致随后优先考虑疫苗接种者。此外，除了每年为美国消费生产 80-9000 万剂 TIV 之外，激增产能也有限，这将在大流行爆发时对疫苗生产构成限制。目前世卫组织针对禽类 H5N1 流感病毒感染和死亡的第三阶段大流行警报状态鼓励了新疫苗技术的开发，该技术能够在严格压缩的时间内生产大量剂量。由于不可能在流感爆发之前预测确切的病毒株，因此需要快速的疫苗生产能力才能及时应对流感大流行。这项研究的最终目标是开发一种能够在很短的时间内生产数百万剂量的基于血凝素 (HA) 的 DNA 疫苗的制造系统。利用 Vical 公司正在开发的新型制造技术，在获得新出现的 HA 基因组序列后的几天到几周内，将可以针对新出现的流感病毒株生产出基于 HA 的 DNA 疫苗。此外，该生产系统将在大流行期间用于生产每年季节性三价疫苗，而不受当前基于鸡蛋的程序的限制。本提案目前的目的是开发和表征基于聚合酶链式反应 (PCR) 的制造系统，该系统可以快速生产包含编码流感 HA 基因的大量线性 DNA 表达盒 (LEC) 的疫苗剂量。