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

无特定病原体狒狒研究资源 (SPFBRR) - 行政补充

• 批准号: 10399105
• 负责人: Joe H. Simmons
• 金额: $ 49.99万
• 依托单位: UNIVERSITY OF TX MD ANDERSON CAN CTR
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-08-15 至 2023-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10399105
• 关键词: 2019-nCoV; ACE2; Adenovirus Vector; Administrative Supplement; Antibodies; Antibody Formation; Antibody Repertoire; Antigens; Antisense Oligonucleotide Therapy; Award; B-Lymphocytes; Binding; Binding Proteins; Biological Markers; Biology; COVID-19; COVID-19 testing; COVID-19 vaccination; Cell Line; Cells; Clinical; Cold Chains; Development; Disease; Dose; Encapsulated; Engineering; Epithelial Cells; FDA approved; Funding; Future; Glycoproteins; Goals; Human; Immune; Immune response; Immunity; Immunize; Immunologic Memory; Laboratories; Lead; Logistics; Lung; Malignant neoplasm of pancreas; Messenger RNA; Molecular Conformation; Mus; Papio; Parents; Pathway interactions; Physiological; Prevention; Primates; Production; Property; Proteins; Regimen; Reporting; Resources; Role; Route; SARS coronavirus; SARS-CoV-2 B.1.1.7; SARS-CoV-2 infection; SARS-CoV-2 pathogenesis; SARS-CoV-2 spike protein; Severe Acute Respiratory Syndrome; Small Interfering RNA; Surface; T-Lymphocyte; Testing; Therapeutic; Tropism; University of Texas M D Anderson Cancer Center; Vaccine Design; Vaccines; Validation; Variant; Viral; Viral Proteins; Virulent; Virus; Virus Shedding; Work; antigen processing; efficacy testing; engineered exosomes; exosome; extracellular vesicles; flexibility; germ free condition; immunogenicity; improved; in vivo; in vivo evaluation; large scale production; lead candidate; nanoparticle; neutralizing antibody; novel vaccines; phase I trial; preservation; response; success; uptake; vaccine development; vaccine evaluation; virology

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.

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。