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

这个小企业技术转让（STTR）第一阶段项目的更广泛的影响/商业潜力改善了从流感开始的病毒性疾病的治疗。在美国，每年季节性流感感染900 - 3500万人，导致56,000人死亡，耗资871亿美元。 拟议的技术有可能产生更快速的保护，扩大病原体/变异体的覆盖范围，并延长流感疫苗和其他疫苗提供的保护寿命。这种额外的保护将降低由于死亡率/发病率造成的高医疗保健成本和生产力损失。这项技术有可能作为一种快速部署的预防或疫苗佐剂，以增强保护和减少必要的疫苗剂量，扩大可及性并提供更及时的反应。虽然疫苗代表了重大的医学成功，但事实证明，一些疾病难以解决，包括季节性和大流行性流感、结核病（TB）、疟疾、丙型肝炎病毒（HCV）和艾滋病毒。提高这些疾病的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递的抗原的免疫应答。所提出的技术具有直接和通过异源免疫增强疫苗针对广泛感染的功效的潜力，因为向卡介苗（BCG）中添加“干扰素基因刺激因子”（STING）激动剂过量生产具有双重目的：它增强了已知由BCG赋予的巨噬细胞的训练免疫力，并促进关键的抗病毒IFN-I应答。本项目的主要目的是：1）优化BCG-STING生产的培养基和冻干; 2）评价BCG-STING作为H1N1流感疫苗佐剂的免疫学效果; 3）评价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，同时还提供内在的抗病毒免疫力。该奖项反映了NSF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.