Wallace H. Coulter Department of Biomedical Engineering, Georgia Tech and Emory University, Atlanta, GA, USA.
New Iberia Research Center, University of Louisiana at Lafayette, Lafayette, LA, USA.
Nat Biomed Eng. 2019 May;3(5):371-380. doi: 10.1038/s41551-019-0378-3. Epub 2019 Apr 1.
Visualization of the spatio-temporal trafficking of vaccines after their delivery would help evaluate the efficacy of candidate formulations and aid their rational design for preclinical and translational studies. Here, we show that a dual radionuclide-near-infrared probe allows for quantitative, longitudinal and non-invasive monitoring, via positron emission tomography-computed tomography and near-infrared imaging of cynomolgus macaques, of the trafficking dynamics to draining lymph nodes of a model messenger RNA vaccine labelled with the probe. After intramuscular administration of the vaccine to the monkeys, we observed the dynamics of the mRNA vaccine at the injection site and in the draining lymph nodes, performed cellular analyses of the involved tissues using flow cytometry and identified through immunofluorescence that professional antigen-presenting cells are the primary cells containing the injected mRNA and encoding the antigen. This approach may reveal spatio-temporal determinants of vaccine efficacy in preclinical and translational studies employing large mammals.
疫苗接种后，对其时空转运进行可视化，有助于评估候选配方的功效，并为临床前和转化研究中疫苗的合理设计提供帮助。在这里，我们展示了一种双放射性核素-近红外探针，通过正电子发射断层扫描-计算机断层扫描和近红外成像，对猕猴引流淋巴结中模型信使 RNA 疫苗的转运动力学进行定量、纵向和非侵入性监测。在将疫苗肌肉内给药给猴子后，我们观察了注射部位和引流淋巴结中 mRNA 疫苗的动力学，使用流式细胞术对涉及的组织进行了细胞分析，并通过免疫荧光鉴定出专业的抗原呈递细胞是主要含有注射 mRNA 并编码抗原的细胞。这种方法可能揭示使用大型哺乳动物进行临床前和转化研究中疫苗功效的时空决定因素。
