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

基本信息

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
项目类别：
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

项目摘要

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.

项目摘要使用纳米颗粒封装了COVID-19疫苗接种mRNA有效载荷的最新成功已经将外泌体的领域充满活力，作为新型疫苗剂。外泌体（40-180nm），在病毒生物学中积极研究了病毒大小并由所有细胞脱落的细胞外囊泡。据报道使用外泌体改善疫苗的免疫原性（包括SARS-COV）可能由于它们在体内的稳定性增强，免疫细胞的质量，增强的摄取和抗原加工和独特的类似病毒的呈现，构象完整的抗原在其上表面，这是SARS COV-2峰糖蛋白（SC2S）所必需的特征抗原性。此外，外泌体具有独特的特性，可提供siRNA/ASO 治疗有效载荷（TP），这是MDACC胰腺癌和FDA的策略获得I期试验（NCT03608631）的批准。利用我们的良好制造实践（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呈现表面SC2S蛋白，旨在产生一种旨在容易的疫苗可以与其他SARS互换，过去或将来。工程外泌体，exovax-sc2s，当前的SC2在其表面上，并将mRNA包装在峰值蛋白上。在此管理中补充，我们还将测试Exovax-SC2在引起B和T细胞免疫中的功效作为狒狒的长期抗体产生。该物种最适合测试这本小说疫苗方法是由于其有症状向SARS COV-2和类似抗体的症状表现出来曲目作为人类。行政补充剂融合了西蒙斯的专业知识和 Kalluri实验室完成了拟议的研究。