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

疫苗是用佐剂配制的，以刺激免疫系统，使疫苗可以更有效地预防疾病。我们的目标是创造一种佐剂配方，克服了许多佐剂的局限性-定制免疫反应以获得所需的免疫结果。具体来说，我们的目标是减少炎症和副作用，并提高流感疫苗的抗体水平。在我们之前的佐剂发现合同中，我们发现当一种叫做巴非替尼的分子与商业疫苗或传统佐剂结合使用时，巴非替尼可以增加抗体滴度或降低炎症，或两者兼有。与NIAID的新合同是改进巴非替尼配方和生产更好佐剂的一个机会。我们将与Inimmune公司合作，将我们的分子Bafetinib与他们的分子ni -4001结合起来。由于其强烈的刺激特性，易于改变的化学结构，以及Inimmune在佐剂开发方面的广泛专业知识，INI-4001很有希望。我们将共同开发由巴非替尼和ni -4001组成的佐剂系统。我们将开发巴非替尼与ni -4001（一种合成的TLR7/8激动剂）联合使用，通过联合制剂或作为单独的辅助添加剂。使用靶向合成修饰的巴非替尼，我们将改善配方，分子组成，稳定性和活性在先前审查的疫苗模型。我们的预期结果包括在我们称为“辅助系统”的新配方中，优化了含有ni -4001的巴非替尼亲本结构的新分子组成。这些佐剂系统将使用脂质体和水包油乳液来定位成分。我们将把新系统的性能与几个现有疫苗平台进行比较。我们将根据重复的性能和毒性测试的结果对配方进行迭代和改进。目的是优化最有希望的配方，以开发最终的主要候选药物。我们将在雪貂挑战流感模型中测试主要候选药物。我们还将测试主要候选产品在更大规模上的生产效果。这些知识将提高我们的研究从小规模实验室到使用标准良好生产规范的生产规模的转化。

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.