Modeling the kinetics of lymph node retention and exposure of a cargo protein delivered by biotin-functionalized nanoparticles

模拟生物素功能化纳米粒子运送的货物蛋白在淋巴结中滞留和暴露的动力学

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作者:Paul R Hartmeier, Jessica L Kosanovich, Ketki Y Velankar, Sarah M Ostrowski, Emelia E Busch, Madeline A Lipp, Kerry M Empey, Wilson S Meng

Significance

Development of safe and effective subunit vaccines depends on effective formulations that render optimized exposure and colocalization of antigens and adjuvants. In this work, we utilize a nanoparticle system which features self-adjuvanting properties and allows for surface loading of recombinant protein antigens. Using in vivo imaging, we demonstrated prolonged co-localization of the antigen and adjuvant particles in draining lymph nodes and provided evidence of B cell activation for up to 21 days following subcutaneous injection. A pharmacokinetic model was developed as a step towards bridging the translational gap between particulate-based vaccines and observed outcomes. The results have implications for the rational design of particle-based vaccines.

Statement of significance

Development of safe and effective subunit vaccines depends on effective formulations that render optimized exposure and colocalization of antigens and adjuvants. In this work, we utilize a nanoparticle system which features self-adjuvanting properties and allows for surface loading of recombinant protein antigens. Using in vivo imaging, we demonstrated prolonged co-localization of the antigen and adjuvant particles in draining lymph nodes and provided evidence of B cell activation for up to 21 days following subcutaneous injection. A pharmacokinetic model was developed as a step towards bridging the translational gap between particulate-based vaccines and observed outcomes. The results have implications for the rational design of particle-based vaccines.

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