I-Corps: A disease-agnostic platform for enhanced vaccine immunogenicity using live microbial vectors

I-Corps：使用活微生物载体增强疫苗免疫原性的疾病不可知平台

• 批准号: 2341293
• 负责人: Aditya Kunjapur
• 金额: $ 5万
• 依托单位: University of Delaware
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-11-15 至 2024-04-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2341293&HistoricalAwards=false
• 关键词: Corps; disease; agnostic; platform; enhanced

The broader impact/commercial potential of this I-Corps project is the development of a disease agnostic platform for the creation of prophylactic and therapeutic vaccines. For diseases ranging from cancer to pathogenic bacteria, weak immunogenicity or tolerance of antigens limits their practical targeting in vaccines. Using the proposed live bacterial vaccine platform and nitrated antigen technology, it may be possible to unlock these antigens as targets. The proposed platform may be used for developing vaccines against diseases lacking current vaccines or diseases with immunotherapeutic solutions with limited efficacy. If successful, it may be possible to create commercial products that will save lives and reduce patient and health care burden.This I-Corps project is based on the development of a technology to enable the vaccination of antigens with weak natural immunity. Several diseases may benefit from immunotherapies or vaccines that can target weakly immunogenic but highly conserved antigens. Bacterial vectors have been developed that autonomously produce proteins with selective introduction of nitro functionalization at desired sites by using metabolic engineering, chemical engineering, and protein engineering. Studies have demonstrated that protein nitration may result in an amplification of CD4+ T cell immune response with enhancement for both bacterial and cancer-associated antigens. This strategy uses non-standard amino acid (nsAA)-based technology. To date, commercial endeavors involving nsAAs focused on using bio-orthogonal functional groups for purposes of reactivity or stability. Here nsAA technology is used in an alternative direction, the improved immunogenic response in vaccines. In addition, the proposed technology combines metabolic synthesis of nsAAs and incorporation into protein antigens, which may circumvent limitations toward nitrated protein synthesis (namely, transport given the intracellular synthesis) and delivery (given bacterial synthesis).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.

这个i-Corps项目的更广泛的影响/商业潜力是开发一个疾病未知平台，用于创建预防性和治疗性疫苗。对于从癌症到致病菌的各种疾病，弱的免疫原性或对抗原的耐受性限制了它们在疫苗中的实际靶向。使用拟议的活细菌疫苗平台和硝化抗原技术，可能会解锁这些抗原作为靶标。建议的平台可用于开发针对当前缺乏疫苗的疾病或具有有限疗效的免疫治疗方案的疾病的疫苗。如果成功，有可能创造出拯救生命、减轻患者和医疗负担的商业产品。i-Corps项目基于一种技术的开发，能够对自然免疫力较弱的抗原进行疫苗接种。几种疾病可能受益于针对免疫原性较弱但高度保守的抗原的免疫疗法或疫苗。利用代谢工程、化学工程和蛋白质工程，细菌载体已经被开发出来，通过在所需位置选择性地引入硝基官能化来自主生产蛋白质。研究表明，蛋白质硝化可导致CD4+T细胞免疫反应的放大，从而增强细菌和癌症相关抗原。这一战略使用了基于非标准氨基酸(NSAA)的技术。到目前为止，涉及NSA的商业努力主要集中在使用生物正交官能团来实现反应性或稳定性的目的。在这里，NSAA技术被用于另一个方向，即改进疫苗的免疫原性反应。此外，拟议的技术结合了新陈代谢合成nsAs和整合到蛋白质抗原中，这可能绕过硝化蛋白质合成(即考虑到细胞内合成)和传递(考虑到细菌合成)的限制。这一奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。