Nanoparticle Vaccines Adopting Virus-like Features for Enhanced Immune Potentiation

Chattopadhyay, Saborni; Chen, Jui-Yi; Chen, Hui-Wen; Hu, Che-Ming Jack

Viruses and virus-like nanoparticulates can accumulate in lymph nodes via both cell-mediated lymphatic delivery and convective lymphatic transport. The cell-mediated transport is mediated primarily by migratory dendritic cells, which take up antigens outside of the lymphatic system (i.e. skin and lung) and enter lymph nodes via either high endothelial venules or lymph vessels [132, 133] . In comparison to small protein antigens, viruses and nanoparticle vaccines are more favorable to this hitchhiking mechanism. Their particulate nature promotes receptor-mediated, complement-mediated, or other intracellular uptake mechanisms [134, 135] . Antigens associated with nanocarriers are routinely observed to be more efficiently uptaken by dendritic cells compared to soluble antigens, thereby enabling more effective lymph node delivery and cross presentation [128, [136] [137] [138] [139] . On the other hand, the nanoscale morphology of viruses and virus-like particulates allows them to move freely in lymphatic vessels to draining lymph nodes. Upon lymph node entry, a special subset of macrophages is responsible for the capture of these nanoparticulates. In a study on lymphatic tracking of viruses by Junt et al., macrophages in the subcapsular sinus and in the medulla of lymph nodes were shown to be responsible for the lymph node accumulation of subcutaneously administered inactivated vesicular stomatitis virus, adenovirus, and vaccinia virus [140] . Depletion of these macrophages resulted in an enhanced virus level that circulated back to the blood, highlighting both viruses' convective transport in the lymphatic system and the macrophages' role in virus filtration. This gatekeeper function by the lymph node-resident macrophages serves to limit blood-borne infection and promote immune processing.