Quantitative biodistribution of viral nanoparticles by nuclear imaging

病毒样颗粒(VLP)代表了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。VLP由蛋白质壳组成，蛋白质壳上点缀着针对疫苗打算控制的任何疾病的蛋白质短链。VLP看起来像病毒，容易被人体免疫系统识别，但它们缺乏核心遗传物质，使它们不具传染性和无法复制。开发基于核成像的可靠而有效的定量生物分布方法，是发展旨在建立免疫反应强度与活体中病毒样颗粒局部存在之间强烈相关性的中长期研究项目的先决条件。该项目将使开发一种有效的方法a)用放射性同位素标记VLP用于正电子发射断层扫描(PET)，B)通过尺寸排除层析(SEC)纯化如此标记的VLP，3)提供注射在小鼠模型中的放射性标记VLP的PET生物分布。这一短期研究项目将提供以下关键信息，对于计划后续的VLP生物分布研究是必要的：放射性标记参数(螯合、螯合结合反应时间、温度、螯合挑战)；SEC纯化参数(最大待洗脱VLP的质量；洗脱动力学；洗脱轮廓；SEC产生的放射性废物的处理；保留VLP功能的参数；待注入的放射性标记VLP的最小质量和活性，以达到可接受的PET生物分布轮廓。在这个短期项目结束时，该公司将获得一套完整的VLP在体内的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基于VLP的新疫苗的验证。

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.