SBIR Phase I: Genetically Engineered BCG as a Microbe-Based Platform for Vaccination Against COVID-19

这项小型企业创新研究（SBIR）第一阶段项目的更广泛影响/商业潜力是开发一种安全和负担得起的COVID-19疫苗接种技术，在管理其他传染病方面具有更广泛的用途。 新的平台是基于修饰的细菌，作为结核病的安全儿科免疫接种有着悠久的历史。预计该技术将显示出热稳定性，安全性，成本效益和易于大规模生产。它可用于儿童和高危人群，包括急救人员、老年人和有基础疾病的人。这也可以在新兴和弱势环境中提供。 拟议的项目能够实现一种基于重组BCG细菌（rBCG）的新型微生物疫苗平台，该细菌被工程化以靶向SARS-CoV-2并预防COVID-19。 本项目的目标是开发表达SARS-CoV-2蛋白片段的BCG，这可能导致诱导针对SARS-CoV-2特异性抗原的适当免疫应答。对于该项目，将根据其生物学特性选择具有最高病毒多肽分泌和持久表达水平的新rBCG候选物并进行优先排序。将在动物模型中评价rBCG疫苗的安全性和免疫原性。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 Innovation Research (SBIR) Phase I project is to develop a safe and affordable COVID-19 vaccination technology, with broader utility in managing other contagious diseases. The new platform is based on modified bacteria, with a long history as a safe pediatric immunization for tuberculosis. The proposed technology is expected to show heat-stability, safety, cost-effectiveness, and ease of mass production. It can be used for children and at-risk groups including first responders, the elderly, and those with underlying conditions. This can be delivered in emerging and disadvantaged environments as well. The proposed project enables a novel microbial vaccine platform based on recombinant BCG bacteria (rBCG) engineered to target SARS-CoV-2 and protect against COVID-19. The goal of this project is to develop BCG that expresses SARS-CoV-2 protein fragments, which could lead to the induction of appropriate immune responses against SARS-CoV-2 specific antigens. For this project, new rBCG candidates with the highest secretion and durable expression levels of viral polypeptides will be selected and prioritized, based on their biological properties. The rBCG vaccines will be evaluated for safety and immunogenicity in animal models. Promising candidates that show no adverse events and induce robust T-cell and antibody responses will be selected for future preclinical studies.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.