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.

虽然金黄色葡萄球菌 (SA) 通常无症状地寄生在健康人的皮肤和鼻子上对于人类来说，血液、骨骼、皮肤和肺部以及其他部位的感染可能会导致严重的疾病通过目前批准的治疗，大约三分之一的患者被诊断出患有这种疾病。 SA菌血症导致的每年死亡人数比艾滋病毒、结核病和病毒性肝炎还要多该 R01 将开发一种注射疫苗长效制剂，其中包括：(a) 先前发表的阳离子疫苗。聚合物将阴离子自我复制 mRNA (SR-mRNA) 疫苗凝结并中和电荷纳米尺寸的颗粒（即“聚合复合物”）然后被纳入（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）的可注射生物降解凝胶。临时 CS-Alg 库可完全生物降解为无毒副产品，并被本项目消除。将产生一种一次性应用的自我免疫生物材料技术，其免疫效果优越与重复全身推注相比。