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.

项目概要阿片类药物使用障碍（OUD）和相关的阿片类药物过量是日益严重的公共卫生危机， 2021 年，仅在美国就有 80,000 例阿片类药物过量相关死亡，这一数字令人震惊。当前治疗策略的可用性，包括治疗阿片类药物使用障碍的药物和药物治疗最近，阿片类药物过量继续以惊人的速度猛增。提议将针对阿片类药物的疫苗作为应对日益严重的危机的新干预措施。靶向阿片类药物已使用传统的蛋白质载体方法开发出来，并正在进入人类该研究项目的总体目标是研究 Qβ 噬菌体病毒样的功效。基于颗粒（VLP）的疫苗靶向羟考酮作为预防羟考酮过量的新型治疗方法。噬菌体 VLP 是高度免疫原性的疫苗平台，已被证实安全有效该项目将在 Qβ VLP 结合疫苗的中心假设下进行。靶向羟考酮将为同源药物攻击提供保护，且交叉反应性有限。假设将通过以下具体目标进行调查：具体目标 1：确定使用高效液相色谱法研究免疫药物跨血脑屏障的分布。质谱（HPLC-MS），将测定血液和脑室中的药物浓度具体目标 2：研究 Qβ-羟考酮对静脉注射药物产生的保护作用。利用全身体积描记法 (WBP)，我将研究 Qβ-羟考酮介导的保护作用。静脉药物激发后阿片类药物引起的呼吸抑制。具体目标 3：检查其影响。免疫接种对纳洛酮功效的影响使用体外和体内方法，疫苗的交叉反应性。与阿片受体拮抗剂纳洛酮引发的抗体将一起确定这些目标。专注于为 OUD 提供有效疫苗设计和提供新治疗选择的长期目标患者。