Quantitative biodistribution of viral nanoparticles by nuclear imaging

病毒样颗粒（vlp）是最令人兴奋的新兴疫苗技术之一，可产生有效和持久的免疫保护。VLPs由蛋白质外壳组成，上面布满了疫苗想要控制的任何疾病所特有的蛋白质短链。vlp被制造得看起来像病毒，使它们很容易被人体免疫系统识别，然而，它们缺乏核心遗传物质，使它们不具有传染性，也无法复制。发展一种基于核成像的可靠和有效的定量生物分布方法是开展中长期研究项目的先决条件，这些研究项目旨在建立免疫反应强度与体内局部存在的病毒样颗粒之间的强相关性。该项目将开发一种有效的方法：a)用放射性同位素对VLP进行放射性标记，用于正电子发射断层扫描（PET）； b)通过尺寸排除色谱法（SEC）纯化放射性标记的VLPs； 3)提供注射到小鼠模型中的放射性标记VLPs的PET生物分布。这个短期研究项目将提供以下关键信息，对规划随后的vlp生物分布研究至关重要：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净化参数(max。待洗脱的VLP质量；洗脱动力学;elutionprofile;处理SEC产生的放射性废物)；保留VLP功能的参数；要注射的放射性标记VLP的最小质量和活性，以达到可接受的PET生物分布概况。在这个短期项目结束时，该公司将获得一套完整的VLPs体内pet生物分布方法。该团队将能够计划一个全面的研究项目，目的是将VLPs作为疫苗产品的有效性与PET数据中揭示的几种生物分布特征联系起来。这种方法有可能加速新的基于vlp的疫苗的验证。

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.