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.

项目概要 最近使用纳米颗粒封装 mRNA 有效负载进行 COVID-19 疫苗接种取得了成功 为外泌体作为新型疫苗制剂领域注入了活力。外泌体（40-180nm）， 病毒生物学中正在积极研究病毒大小并由所有细胞脱落的细胞外囊泡。 据报道，使用外泌体来提高疫苗（包括 SARS-Cov）的免疫原性可能 由于其体内稳定性增强、免疫细胞趋向性、吸收和抗原增强 其上构象完整的抗原的加工和独特的、类似病毒的呈现 表面，这一特征被认为是 SARS CoV-2 刺突糖蛋白 (SC2S) 所必需的 抗原性。此外，外泌体具有递送 siRNA/ASO 的独特特性 治疗有效负载 (TP)，MDACC 和 FDA 为胰腺癌开发的策略 批准进行第一阶段试验（NCT03608631）。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，我们最近在外泌体工程和测试方面的努力 呈现表面 SC2S 蛋白，旨在产生一种易于被设计的疫苗 可以与过去或未来的其他 SARS 互换。工程外泌体 ExoVAX-SC2S， 在其表面呈现 SC2S 并封装刺突蛋白的 mRNA。在本行政 补充剂，我们还将测试 ExoVAX-SC2S 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。该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而采用疫苗方法 作为人类的曲目。行政补充结合了西蒙斯和 Kalluri 实验室完成了拟议的研究。