DEVELOPMENT OF VACCINES FOR INFLUENZA USING AN IMMUNO-MODULATOR ADJUVANT AND MULTI-PLATFORM APPROACH

使用免疫调节佐剂和多平台方法开发流感疫苗

• 批准号: 10935797
• 负责人: BRUXANNE EL-KAMMASH
• 金额: $ 196.49万
• 依托单位: UNIVERSITY OF CHICAGO
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-30 至 2028-09-29
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10935797
• 关键词: Adjuvant; Agonist; Antibodies; Antibody titer measurement; Antigens; Chemical Structure; Chemistry; Contractor; Contracts; Development; Disease; Emulsions; Ferrets; Fluzone; Formulation; Goals; Good Manufacturing Process; Immune response; Immune system; Immunologic Stimulation; Immunologics; Immunomodulators; Inflammation; Influenza; Influenza A Virus, H1N1 Subtype; Influenza A Virus, H3N2 Subtype; Influenza B Virus; Knowledge; Laboratories; Liposomes; Messenger RNA; Modeling; Modification; Molecular; Mus; National Institute of Allergy and Infectious Disease; Oils; Outcome; Parents; Performance; Production; Property; RNA vaccine; Recombinants; Research; Structure; System; TLR7 gene; Testing; Toxicity Tests; Toxicology; Translations; Vaccines; Water; efficacy study; immunogenicity; improved; influenza virus vaccine; inhibitor; lead candidate; manufacture; performance tests; prevent; side effect; vaccine development; vaccine platform

Vaccines are formulated with adjuvants to stimulate the immune system so that the vaccine can be more effective at preventing disease. Our goal is to create an adjuvant formulation that overcomes a limitation in many adjuvants - customization of the immune response for a desired immunological outcome. Specifically, our goal is to reduce inflammation and side effects and to increase antibody levels in vaccines used for influenza. In our previous Adjuvant Discovery Contract, we discovered that when a molecule called Bafetinib was combined with a commercial vaccine or traditional adjuvant, Bafetinib can increase antibody titers or lower inflammation, or both. This new contract with the NIAID is an opportunity to improve Bafetinib’s formulation and yield a better adjuvant. We will partner with Inimmune Corporation to combine our molecule, Bafetinib, with their molecule, INI-4001. INI-4001 is promising due to its strong stimulatory properties, readily altered chemical structure, and because Inimmune has extensive expertise in adjuvant development. Together, we will develop an adjuvant system composed of Bafetinib and INI-4001. We will develop Bafetinib in combination with INI-4001 (a synthetic TLR7/8 agonist) through co-formulation or as a stand-alone adjuvant additive. Using targeted synthetic modifications of Bafetinib, we will improve the formulation, molecular composition, stability, and activity in previously vetted vaccine models. Our expected outcomes include optimized formulations of new molecular compositions of the parent structure of Bafetinib with INI-4001 in new formulations we refer to as “adjuvant systems.” These adjuvant systems will use both liposome and oil-in-water emulsion to localize the components. We will compare the performance of our new system to several existing vaccine platforms. We will iterate the formulations and improve them based on results from repeating the performance and toxicity tests. The purpose is to optimize the most promising formulation to develop a final lead candidate. We will test the lead candidate in Ferret challenge models of influenza. We will also test how well the lead candidate can be produced on a larger scale. This knowledge will improve the translation of our research from the small-scale laboratory to production-scale using standard Good Manufacturing Practices.

疫苗由调节器配制，以刺激免疫系统，以便疫苗可以更有效预防疾病。我们的目标是创建一个可调节的公式，该公式克服了许多调节器的限制 - 自定义免疫响应以获得所需的免疫学结果。具体而言，我们的目标是减少感染和副作用，并增加用于影响的疫苗的抗体水平。在我们以前的辅助发现合同中，我们发现，当一种称为Bafetinib的分子与商用疫苗或传统调整结合使用时，Bafetinib可以增加抗体滴度或较低的注射剂，或两者兼而有之。与NIAID的新合同是改善Bafetinib公式并获得更好调整的机会。我们将与Inimmune Corporation合作，将我们的分子Bafetinib与他们的分子INI-4001结合在一起。承诺将INI-4001共同提供，我们将开发一个由Bafetinib和Ini-4001组成的可调节系统。我们将通过共制造或作为独立的可调添加剂来开发与INI-4001（合成TLR7/8激动剂）结合使用的Bafetinib。使用Bafetinib的靶向合成修饰，我们将在先前审查的疫苗模型中改善形成，分子组成，稳定性和活性。我们的预期结果包括Bafetinib与新公式中INI-4001的母体结构的新分子结构的优化公式，我们称为“辅助系统”。这些调整系统将使用脂质体和水中乳液来定位组件。我们将将新系统的性能与几个现有的疫苗平台进行比较。我们将根据重复性能和毒性测试的结果来迭代公式并改进它们。目的是优化开发最终铅候选人的最有希望的公式。我们将在影响力的雪貂挑战模型中测试主要候选者。我们还将测试铅候选人如何更大规模生产。这些知识将使用标准良好的制造实践来改善我们从小型实验室向生产规模的研究的翻译。