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

项目摘要 纳米粒包裹基因载体在新冠肺炎疫苗接种中的研究进展 作为新的疫苗制剂，已经为外切体领域注入了活力。外切体(40-180 nm)， 病毒大小的细胞外小泡在病毒生物学中被活跃地研究。 据报道，使用外切体提高疫苗(包括SARS-CoV)的免疫原性可能会 由于它们增强了体内的稳定性，对免疫细胞的趋向性，增强了摄取和抗原 在其上处理和独特的、类似病毒的构象完整的抗原呈现 表面，被认为是SARS CoV-2刺激性糖蛋白(SC2S)必不可少的特征 抗原性。此外，外切体具有递送siRNA/ASO的独特性质 治疗有效载荷(TP)，这是MDACC和FDA为胰腺癌开发的一种策略 批准进行第一阶段试验(NCT03608631)。利用我们的良好制造规范(GMP) 经过认证的临床级exosome平台，我们最近在工程和测试exosome方面所做的努力 提供表面SC2S蛋白，旨在生产一种易于设计的疫苗 可与其他SARS互换，过去或未来。工程外体ExoVAX-SC2S， 将SC2S呈现在它们的表面，并将其包裹为Spike蛋白的mRNA。在这个管理部门中 补充，我们还将测试ExoVAX-SC2S在诱导B细胞和T细胞免疫方面的效果 因为在浣熊体内产生的抗体是长期的。这个物种最适合测试这部小说 疫苗方法，因为它对SARS CoV-2和类似的抗体有症状 作为人类的剧目。行政副刊结合了西蒙斯和 Kalluri实验室完成拟议的研究。

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.