Specific Pathogen Free Baboon Research Resource (SPFBRR) - Administrative Supplement

项目摘要 最近成功使用纳米颗粒封装mRNA有效载荷用于COVID-19疫苗接种 使外来体作为新型疫苗剂的领域充满活力。外泌体（40 - 180nm）， 病毒大小的细胞外囊泡，由所有细胞脱落，在病毒生物学中被积极研究。 据报道，使用外泌体来提高疫苗（包括SARS-Cov）的免疫原性， 这是由于它们增强的体内稳定性、对免疫细胞的趋向性、增强的摄取和抗原 处理，和独特的，病毒样呈递的构象完整的抗原在他们的 表面，被认为是SARS CoV-2刺突糖蛋白（SC2S）所必需的特征 抗原性此外，外泌体具有递送siRNA/ASO的独特性质， 治疗有效载荷（TP），MDACC和FDA开发的胰腺癌治疗策略 批准用于I期试验（NCT 03608631）。利用我们的良好生产规范（GMP） 经过认证的临床级外泌体平台，我们最近在工程和测试外泌体方面的努力 目的是产生设计成容易被免疫接种的疫苗， 与过去或未来的其他SARS可以互换。工程化的外泌体ExoVAX-SC2S， 在它们的表面上呈递SC2S并封装刺突蛋白的mRNA。本行政 作为补充，我们还将测试ExoVAX-SC2 S在引发B细胞和T细胞免疫方面的功效 狒狒体内长期产生抗体。这个物种最适合测试这部小说 由于其对SARS CoV-2和类似抗体的症状表现， 和人类一样。行政补充凝聚了西蒙斯的专业知识， 完成拟定研究的Kendi实验室。

Project Summary Recent successes using nanoparticles encapsulating mRNA payload for COVID-19 vaccination have energized the field of exosomes as novel vaccine agents. Exosomes (40-180nm), extracellular vesicles of the size of a virus and shed by all cells, are actively studied in viral biology. The reported use of exosomes to improve immunogenicity of vaccines (including SARS-Cov) may result from their enhanced stability in vivo, tropism for immune cells, enhanced uptake and antigen processing, and unique, virus-like presentation of a conformationally intact antigen on their surface, a feature recognized as essential for SARS CoV-2 spike glycoprotein (SC2S) antigenicity. Further, exosomes present with the unique property to deliver a siRNA/ASO therapeutic payload (TP), a strategy developed at MDACC for pancreatic cancer and FDA approved for Phase I trial (NCT03608631). Leveraging our good manufacturing practices (GMP) certified clinical grade exosomes platform, our recent efforts in engineering and testing exosomes presenting with surface SC2S protein aimed to yield a vaccine designed to be readily interchangeable to other SARS, past or future. The engineered exosomes, ExoVAX-SC2S, present SC2S on their surface and encapsulate mRNA for the spike protein. In this administrative supplement, we will test the efficacy of ExoVAX-SC2S in eliciting B- and T cell immunity as well as long term antibody production in Baboons. The species is best suited for testing this novel vaccine approach due to its symptomatic presentation to SARS CoV-2 and a similar antibody repertoire as humans. The administrative supplement coalesces the expertise of Simmons and Kalluri laboratories to accomplish the proposed studies.