Quantitative biodistribution of viral nanoparticles by nuclear imaging

通过核成像定量病毒纳米粒子的生物分布

• 批准号: 509485-2017
• 负责人: Fortin, MarcAndré
• 金额: $ 1.82万
• 依托单位: Université Laval
• 依托单位国家: 加拿大
• 项目类别: Engage Grants Program
• 财政年份: 2017
• 资助国家: 加拿大
• 起止时间: 2017-01-01 至 2018-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=639465
• 关键词: Quantitative; biodistribution; viral; nanoparticles; nuclear

Virus-Like Particles (VLPs) represent one of the most exciting emerging vaccine technologies for generatingeffective and long-lasting immune protection. VLPs consist of protein shells studded with short strands of theproteins specific to whatever disease the vaccine is intended to control. VLPs are made to look like a virus,allowing them to be recognized readily by the body's immune system, however, they lack the core geneticmaterial, making them non-infectious and unable to replicate.The development of a reliable and efficient quantitative biodistribution methodology based on nuclear imaging,is a prerequisite for the development of mid and long-term research projects aiming at establishing strongcorrelations between the strength of the immune response, and the local presence of virus-like particles in vivo.This project will enable the development of an efficient methodology a) to radiolabel VLP with radioisotopesfor positron emission tomography (PET), b) to purify thus-radiolabeled VLPs by size-exclusionchromatography (SEC), 3) to provide PET biodistribution of radiolabeled VLPs, injected in a mouse model.This short-term research project will provide the following key information, essential for planning subsequentVLP biodistribution studies: radiolabeling parameters (chelate, chelate binding reaction time, temperature,chelation challenge); SEC purification parameters (max. mass of VLP to be eluted; elution kinetics; elutionprofile; handling of radioactive waste produced by SEC); parameters for preserving VLP functionality;minimum mass and activity of radiolabeled VLP to be injected, to reach acceptable PET biodistributionprofiles. At the end of this short-term project, the company will have access to a complete methodology for thePET biodistribution of VLPs in vivo. The team will be able to plan a full-scale research project, with the aim ofcorrelating the effectiveness of VLPs as vaccination products, with several biodistribution signatures revealedin PET data. This methodology has the potential to accelerate the validation of new VLP-based vaccines.

病毒样颗粒（VLP）代表了最令人兴奋的新兴疫苗技术之一，用于产生有效和持久的免疫保护。VLP由蛋白质外壳组成，外壳上布满了疫苗所要控制的任何疾病的特异性蛋白质短链。VLP看起来像一种病毒，使它们能够被人体的免疫系统识别，然而，它们缺乏核心遗传物质，使它们不具有感染性，无法复制。是中长期发展的前提-长期研究项目旨在建立免疫反应强度之间的强相关性，以及体内病毒样颗粒的局部存在。该项目将能够开发一种有效的方法a）用放射性同位素放射性标记VLP用于正电子发射断层扫描（PET），B）通过尺寸排阻色谱法（SEC）纯化如此放射性标记的VLP，3）提供注射到小鼠模型中的放射性标记的VLP的PET生物分布。放射性标记参数（螯合物、螯合物结合反应时间、温度、螯合挑战）; SEC纯化参数（最大待洗脱的VLP质量;洗脱动力学;洗脱曲线; SEC产生的放射性废物的处理）;保存VLP功能的参数;待注射的放射性标记VLP的最小质量和活性，以达到可接受的PET生物分布特征。在这个短期项目结束时，该公司将获得一个完整的方法，用于体内VLP的PET生物分布。该团队将能够计划一个全面的研究项目，目的是将VLP作为疫苗接种产品的有效性与PET数据中揭示的几个生物分布特征相关联。这种方法有可能加速验证新的基于VLP的疫苗。