Bacteriophage virus-like particle based vaccines against oxycodone

基于噬菌体病毒样颗粒的羟考酮疫苗

基本信息

批准号：
10750819
负责人：
Isabella Romano
金额：
$ 3.71万
依托单位：
UNIVERSITY OF NEW MEXICO HEALTH SCIS CTR
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-09-01 至 2026-07-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10750819
关键词：
American Animal Model Animals Antibodies Antibody Avidity Antibody Response Bacteriophages Binding Blood Blood - brain barrier anatomy Brain Carrier Proteins Cessation of life Clinical Trials Conjugate Vaccines Data Development Dose Drug Exposure Drug Targeting Effectiveness Engineering Enzyme-Linked Immunosorbent Assay Fellowship Fentanyl Foundations Goals Haptens High Pressure Liquid Chromatography Human Immunization Immunize Immunology In Vitro Individual Intervention Intravenous Investigation Keyhole Limpet Hemocyanin Knowledge Mass Spectrum Analysis Mediating Modeling Naloxone Opioid Opioid Antagonist Opioid Receptor Overdose Oxycodone Patients Pharmaceutical Preparations Phase Prevention Public Health Rattus Research Research Project Grants Research Proposals Route Safety Serum Severities Structure Surface Techniques Tetanus Toxoid United States Vaccinated Vaccination Vaccine Design Vaccines Ventilatory Depression Virus-like particle Whole Body Plethysmography blood-brain barrier crossing chemical conjugate clinically relevant combat cross reactivity drug distribution exposure route immunogenic improved in vivo interest liquid chromatography mass spectrometry medication for opioid use disorder medication-assisted treatment novel novel strategies novel therapeutic intervention novel vaccines opioid epidemic opioid overdose opioid use disorder pre-clinical prescription opioid abuse prevent protective efficacy self assembly skills subcutaneous translational applications treatment strategy vaccine development vaccine platform vaccinology

项目摘要

PROJECT SUMMARY Opioid use disorder (OUD) and associated opioid overdoses are public health crises of increasing severity, reflected by a staggering 80,000 opioid overdose associated deaths in the United States alone in 2021. Despite the availability of current treatment strategies including medications for opioid use disorder and medication assisted treatment (MOUD and MAT), opioid overdoses continue to skyrocket at an alarming rate. Recently, vaccines targeting opioids were proposed as a novel intervention to combat the growing crisis. Vaccines targeting opioids have been developed using traditional protein carrier approaches and are entering human clinical trials. The overall goal of this fellowship is to investigate the efficacy of a Qβ bacteriophage virus-like particle (VLP) based vaccine targeting oxycodone as a novel treatment to prevent oxycodone overdose. Bacteriophage VLPs are highly immunogenic vaccine platforms that are well-established to be safe and effective in humans. This project will be conducted under the central hypothesis that a Qβ VLP conjugated vaccine targeting oxycodone will offer protection upon cognate drug challenge with limited cross-reactivity. This hypothesis will be investigated by the following specific aims: Specific Aim 1: Determine the impact of immunization on drug distribution across the blood-brain barrier. Using high-performance liquid chromatography mass spectrometry (HPLC-MS), drug concentrations will be determined in the blood and brain compartments of immunized animals. Specific Aim 2: Investigate protection elicited by Qβ-oxycodone upon intravenous drug challenge. Utilizing whole-body plethysmography (WBP), I will investigate Qβ-oxycodone mediated protection from opioid induced respiratory depression upon intravenous drug challenge. Specific Aim 3: Examine the impact of immunization on naloxone efficacy. Using in-vitro and in-vivo approaches, the cross-reactivity of vaccine elicited antibodies with the opioid receptor antagonist naloxone will be determined. Together, these aims are focused on the long-term goal to inform effective vaccine design and offer new treatment options for OUD patients.

项目摘要阿片类药物使用障碍（OUD）和相关的阿片类药物过量是严重程度增加的公共卫生危机，仅在2021年，仅在美国，仅美国就会发生惊人的80,000例阿片类药物过量相关的死亡。尽管当前治疗策略的可用性，包括用于阿片类药物使用障碍和药物的药物辅助治疗（MOUD和MAT），阿片类药物过量继续以惊人的速度飙升。最近，提出靶向阿片类药物的疫苗作为应对日益增长的危机的新干预措施。疫苗靶向阿片类药物是使用传统蛋白质载体方法开发的，并且正在进入人类临床试验。该团契的总体目标是研究类似Qβ噬菌体病毒的效率基于粒子（VLP）靶向羟考酮作为一种新的治疗方法，以防止羟考酮过量。噬菌体VLP是高度免疫原性疫苗平台，已建立良好的安全性可安全有效在人类中。该项目将在QβVLP偶联疫苗的中心假设下进行。靶向羟考酮将在有限的交叉反应性方面对同源药物挑战提供保护。这假设将通过以下特定目的进行研究：具体目的1：确定的影响对血脑屏障的药物分布的免疫。使用高性能液相色谱质谱法（HPLC-MS），将在血液和脑部室中确定药物浓度免疫动物。特定目标2：研究Qβ-氧气辅酶对静脉注射药物产生的保护挑战。利用全体体积学（WBP），我将研究Qβ-氧酮介导的保护阿片类药物引起的呼吸道抑郁症受到静脉药物挑战。特定目标3：检查影响纳洛酮效率的免疫。使用体外和体内方法，疫苗的交叉反应性将确定用阿片受体拮抗剂纳洛酮引起的抗体。在一起，这些目标是专注于长期目标，以告知有效的疫苗设计并为Oud提供新的治疗选择患者。