STTR Phase I: Recombinant BCG as a novel immunoadjuvant for viral infections

这项小企业技术转让（STTR）第一阶段项目具有更广泛的影响/商业潜力，可改善病毒性疾病的治疗，首先是流感。每年季节性流感感染900 - 3500万人，在美国造成56,000人死亡，造成871亿美元的损失。拟议的技术有可能产生更快速的保护，扩大病原体/变异的覆盖范围，并延长流感疫苗和其他疫苗提供的保护的寿命。这种额外的保护将降低高昂的医疗成本和由于死亡率/发病率造成的生产力损失。这项技术有潜力作为一种可快速部署的预防性或疫苗佐剂，以加强保护并减少必要的疫苗剂量，扩大获取途径并提供更及时的反应。这个小企业技术转让第一阶段项目推进了下一代疫苗佐剂平台。虽然疫苗是一项重大的医学成就，但事实证明，一些疾病难以应对，包括季节性流感和大流行性流感、结核病、疟疾、丙型肝炎病毒和艾滋病毒。提高这些疾病疫苗效力的一种方法是使用佐剂来加强对通过疫苗接种呈现的抗原的免疫反应。所提出的技术有可能直接或通过异源免疫增强疫苗对多种感染的效力，因为在卡介苗（BCG）中添加过量生产的“干扰素基因刺激剂”（STING）激动剂具有双重目的：它增强了已知由卡介苗赋予的巨噬细胞的升高的训练免疫，并促进关键的抗病毒IFN-I反应。本项目的主要目标是：1)优化制备BCG-STING的培养基和冻干工艺；2)评价BCG-STING作为H1N1流感疫苗佐剂的免疫效果；3)评估BCG-STING作为H1N1疫苗佐剂的保护作用。这将为继续开发这种新型重组卡介苗作为一种增强疗效的佐剂提供概念证明，这种佐剂也提供内在的抗病毒免疫。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

The broader impact /commercial potential of this Small Business Technology Transfer (STTR) Phase I project improves treatment of viral conditions, starting with influenza. Each year seasonal influenza infects 9–35 million individuals, causes 56,000 deaths in the U.S., and costs $87.1 billion. The proposed technology has the potential to produce more rapid protection, expand pathogen/variant coverage, and extend the longevity of protection afforded by influenza vaccination and other vaccines. This added protection will reduce the high healthcare costs and productivity losses due to mortality/morbidity. This technology has the potential to serve as a rapidly deployable prophylactic or vaccine adjuvant to enhance protection and reduce the necessary vaccine dose, expanding access and providing a timelier response.This Small Business Technology Transfer Phase I project advances a next-generation vaccine adjuvant platform. While vaccines represent a major medical success, several diseases have proven difficult to address, including seasonal and pandemic influenza, tuberculosis (TB), malaria, hepatitis C virus (HCV), and HIV. One way to improve the efficacy of vaccines for these diseases is to use an adjuvant to strengthen the immune response to the antigen presented via vaccination. The proposed technology has the potential to enhance the efficacy of vaccines against a wide range of infections directly and via heterologous immunity because the addition of “Stimulator of Interferon Genes” (STING) agonist overproduction to Bacillus Calmette-Guérin (BCG) serves a dual purpose: it enhances the elevated trained immunity of macrophages already known to be conferred by BCG and promotes critical antiviral IFN-I responses. The key objectives for this project are: 1) Optimize media and lyophilization for manufacturing of BCG-STING; 2) Evaluate the immunological effects of BCG-STING as an adjuvant for H1N1 influenza vaccination; and 3) Assess the protective effects of BCG-STING as an adjuvant for H1N1 vaccination. This will provide proof of concept for proceeding with the development of this novel recombinant BCG as an efficacy-boosting adjuvant that also offers intrinsic antiviral immunity.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.