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

基本信息

批准号：
10664048
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
项目类别：
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/10664048
关键词：
3-Dimensional Accounting Adjuvant Affinity Alginates Antibiotics Antibodies Antibody Formation Antibody titer measurement Antigens B-Lymphocytes Bacteremia Bacteria Bacterial Adhesins Binding Biocompatible Materials Bolus Infusion Catheters Cause of Death Cell secretion Cessation of life Charge Chitosan DNA Data Dendritic Cells Diagnosis Disease Dose Exhibits Gel Genes HIV Hospitals 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 Osteomyelitis Particle Size Patients Peptides Persons Phase Polymers Polysaccharides Porosity 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 Transfection Tuberculosis 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 self assembly vaccination outcome vaccine delivery vaccine development vector vector vaccine

项目摘要

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.

葡萄球菌金黄色葡萄球菌（SA）通常不对称地分散了健康的皮肤和鼻子人类，严重疾病可能是由于血液，骨骼，皮肤和肺部感染而引起的，以及导管和假肢设备。有了目前批准的治疗，约有三分之一的患者被诊断出患有 SA细菌屈服，占死亡人数比HIV，结核病和病毒性肝炎更多的死亡人数。合并。该R01将开发可注射的疫苗押金完成：（a）先前发表的阳离子聚合物将阴离子自我复制mRNA（SR-MRNA）疫苗凝结和电荷到纳米尺寸的颗粒（即“多链体”）然后在（b）中纳入我们最近报道的 N-核酸壳壳（S-CS）和氧化算法（O-ALG）的可注射可生物降解的凝胶。最终，临时CS-ALG沉积完全将消除的无毒副产品生物降解。这个项目将产生一种自免疫的生物材料技术，该技术一旦应用于免疫接种相对于重复的全身注射。