Protective vaccine for H5N1 Flu using H5 protein and a novel TLR4 agonist.

使用 H5 蛋白和新型 TLR4 激动剂的 H5N1 流感保护性疫苗。

• 批准号: 8058825
• 负责人: Christopher H Clegg
• 金额: $ 100万
• 依托单位: TRIA BIOSCIENCE CORPORATION
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-25 至 2014-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8058825
• 关键词: Adjuvant; Agonist; Agreement; Animal Model; Antibody Formation; Antigens; Antiviral Agents; Avian Influenza; Avian Influenza A Virus; B-Lymphocytes; Biological Assay; Birds; Budgets; Cessation of life; Clinical; Clinical Research; Communicable Diseases; Complex; Cross-Priming; Cyclic GMP; Data; Development; Disease; Dose; Drug Formulations; Emulsions; Ferrets; Goals; Government; H5 hemagglutinin; Heterophile Antibodies; Human; Immune; Immunity; Infection; Infection prevention; Influenza A Virus, H5N1 Subtype; Injection of therapeutic agent; International; Lead; Macaca; Manufacturer Name; Marketing; Measures; Methodology; Modeling; Mus; Oils; Performance; Phase; Phase I Clinical Trials; Population; Positioning Attribute; Process; Production; Proteins; Reagent; Recombinants; Relative (related person); Risk; Safety; Series; Small Business Innovation Research Grant; T-Lymphocyte; TLR4 gene; Testing; Toxicology; Vaccinated; Vaccine Adjuvant; Vaccine Antigen; Vaccine Design; Vaccines; Vietnam; Viral; Virus; Water; aluminum sulfate; base; combat; commercialization; design; flu; immunogenicity; improved; influenza outbreak; new technology; nonhuman primate; novel; novel vaccines; pandemic disease; pandemic influenza; pandemic preparedness; prevent; research study; response; toll-like receptor 4; tool; vaccine candidate; vaccine safety

DESCRIPTION (provided by applicant): H5N1 is a highly pathogenic avian influenza virus that can cause severe disease and death in humans. H5N1 is spreading rapidly in bird populations world-wide and there is great concern that this virus will begin to transmit between people and cause a global pandemic catastrophe. Vaccines are the cornerstone strategy for combating avian flu but there are complex challenges facing us today including, (1) the inability to manufacture the vast numbers of safe and effective doses needed to prevent infection on a world-wide scale; (2) the fact that the current vaccines are ineffective and require large doses, and (3), virus strains are continually changing, which complicates vaccine strain selection. TRIA Bioscience Corp. is developing a novel adjuvanted vaccine for pandemic H5N1 Flu that should solve many of the scientific and technological barriers confronting this field. The vaccine antigen is recombinant H5 haemagglutinin (rH5), which uses a production process that simplifies many of the manufacturing issues associated with conventional vaccines, and the adjuvant (GLA-SE) that combines two clinically-validated strategies for augmenting vaccine performance, a synthetic Toll-Like Receptor-4 agonist, GLA, and an oil-in-water emulsion, SE. We are building on our compelling Phase I SBIR data by proposing activities leading up through an IND. First, we will compare GLA-SE activity against two simpler GLA-formulations designed to streamline adjuvant development and regulatory approval. Second, we will establish vaccine protection in ferret challenge models and establish safety and immunogenicity end-points in non-human primates. Third, we will manufacture and release cGMP-grade H5 protein and adjuvant, and obtain FDA clearance for a Phase I clinical trial. The results from this study will provide a relevant measure of dose sparing for vaccine manufacturers and inform clinicians about a new tool for inducing broad immunity against drifted strains of H5N1 virus. The US and world governments are investing billions of dollars in pandemic preparedness measures and TRIA will be well-positioned to participate in this market. This vaccine's design is broadly applicable to other infectious diseases, which increases its commercial potential even further. PUBLIC HEALTH RELEVANCE: There is great international concern that the highly pathogenic H5N1 avian influenza virus will cause a pandemic infection resulting in millions of deaths. We are developing an adjuvanted vaccine with new technologies that will streamline manufacturing constraints and prevent H5N1 infection on a global scale.

描述（由申请人提供）：H5N1 是一种高致病性禽流感病毒，可导致人类严重疾病和死亡。 H5N1 病毒正在世界各地的鸟类中迅速传播，人们非常担心这种病毒将开始在人与人之间传播并导致全球大流行灾难。疫苗是抗击禽流感的基石战略，但我们今天面临着复杂的挑战，包括：（1）无法在世界范围内生产预防感染所需的大量安全有效的剂量； (2)现有疫苗效果不佳且需要大剂量；(3)病毒株不断变化，使疫苗株选择变得复杂。 TRIA Bioscience Corp. 正在开发一种针对大流行 H5N1 流感的新型佐剂疫苗，该疫苗将解决该领域面临的许多科学和技术障碍。疫苗抗原是重组 H5 血凝素 (rH5)，它使用的生产工艺简化了与传统疫苗相关的许多制造问题，佐剂 (GLA-SE) 结合了两种经过临床验证的策略来增强疫苗性能，一种合成的Toll 样受体 4 激动剂 GLA 和水包油乳液 SE。我们正在以令人信服的第一阶段 SBIR 数据为基础，提出通过 IND 开展的活动。首先，我们将 GLA-SE 活性与两种更简单的 GLA 制剂进行比较，这些制剂旨在简化佐剂开发和监管审批。其次，我们将在雪貂攻击模型中建立疫苗保护，并在非人类灵长类动物中建立安全性和免疫原性终点。第三，我们将生产和发布cGMP级H5蛋白和佐剂，并获得FDA批准进行I期临床试验。这项研究的结果将为疫苗制造商提供相关的剂量节省措施，并为临床医生提供一种新工具，用于诱导针对 H5N1 病毒漂移株的广泛免疫力。美国和世界各国政府正在投资数十亿美元用于流行病防备措施，TRIA 将处于有利地位以参与该市场。该疫苗的设计广泛适用于其他传染病，这进一步增加了其商业潜力。 公共卫生相关性：国际社会非常担心高致病性 H5N1 禽流感病毒将引起大流行感染，导致数百万人死亡。我们正在开发一种采用新技术的佐剂疫苗，该疫苗将简化生产限制并在全球范围内预防 H5N1 感染。