Injectable Hydrogel Depots for Self-replicating mRNA Vaccine Delivery

用于自我复制 mRNA 疫苗递送的可注射水凝胶库

• 批准号: 10438409
• 负责人: James D. Bryers
• 金额: $ 54.02万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-07-12 至 2026-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10438409
• 关键词: 3-Dimensional; Accounting; Adjuvant; Affinity; Alginates; Antibiotics; Antibodies; Antibody Formation; Antibody titer measurement; Antigen Targeting; Antigens; B-Lymphocytes; Bacteremia; Bacteria; Bacterial Adhesins; Biocompatible Materials; Bolus Infusion; Catheters; Cations; Cause of Death; Cell secretion; Cessation of life; Charge; Chitosan; DNA; Data; Dendritic Cells; Diagnosis; Disease; Dose; Exhibits; Gel; Genes; HIV/TB; Human; Hydrogels; Immune response; Immunity; Immunization; Immunize; Immunoglobulin G; Implant; In Vitro; Individual; Infection; Infectious Skin Diseases; Injectable; Injections; Interferon Type II; Intravenous; Kinetics; Liquid substance; Lung infections; Medical Care Costs; Medical Device; Membrane; Memory B-Lymphocyte; Messenger RNA; Methicillin Resistance; Microbial Biofilms; Modeling; Mus; Nose; Nosocomial Infections; Osteomyelitis; Oxides; Particle Size; Patients; Peptides; Persons; Phase; Polymers; Polysaccharides; Program Development; Prosthesis; Protein Subunits; Publishing; RNA vaccine; Reaction; Reporting; Schiff Bases; Sepsis; Series; Signal Transduction; Site; Skin colonization; Splenocyte; Staphylococcus aureus; Staphylococcus aureus infection; Staphylococcus epidermidis; Subunit Vaccines; Survival Rate; Syringes; System; T cell response; T-Lymphocyte; Technology; Text; United States; Vaccines; Vancomycin; Vancomycin-resistant S. aureus; Viral hepatitis; Virulence Factors; Work; coronavirus disease; crosslink; design; extracellular; in vivo; medical implant; methicillin resistant Staphylococcus aureus; nanoparticle; nanoscale; novel; novel therapeutics; porous hydrogel; pre-clinical research; prevent; response; scaffold; vaccination outcome; vaccine delivery; vaccine development; vector; vector vaccine

While Staphylococcus aureus (SA) commonly asymptomatically colonizes the skin and nose of healthy humans, severe disease can result from infection of the blood, bone, skin, and lungs, as well as sites of catheters and prosthetic devices. With currently approved therapy, about one-third of patients diagnosed with SA bacteremia succumb, accounting for more annual deaths than HIV, tuberculosis, and viral hepatitis combined. This R01 will develop an injectable vaccine depot comprising: (a) previously published cationic polymers to condense and charge neutralize anionic self-replicating mRNA (SR-mRNA) vaccines into nanometer-sized particles (i.e., “polyplexes”) that are then incorporated within (b) our recently reported injectable biodegradable gel of N-succinyl-chitosan (S-CS) and oxidized alginate (O-Alg). Ultimately, the temporary CS-Alg depots completely biodegrade into non-toxic by-products that are eliminated. This project will generate a self-immunizing biomaterials technology that is applied ONCE that is superior in immunization versus repeated systemic bolus injections.

虽然金黄色葡萄球菌（SA）通常无症状地定植在健康人的皮肤和鼻子上， 对于人类，严重的疾病可由血液、骨骼、皮肤和肺的感染以及 导管和假体装置。在目前批准的治疗中，大约三分之一的诊断为 SA菌血症死亡，每年死亡人数超过艾滋病毒，结核病和病毒性肝炎 加起来该R 01将开发一种可注射的疫苗储库，其包含：（a）先前公开的阳离子 聚合物，以使阴离子自我复制mRNA（SR-mRNA）疫苗缩合并电荷中和成 纳米尺寸的颗粒（即，“聚合复合物”），然后将其并入（B）我们最近报道的 N-琥珀酰壳聚糖（S-CS）和氧化海藻酸盐（O-Alg）可注射生物降解凝胶。最终 临时CS-Alg储存库完全生物降解成无毒的副产品，并被消除。这个项目 将产生一种自身免疫的生物材料技术，这种技术在免疫方面具有上级的优势， 与重复全身推注相比。