Nanoparticle Vaccines Adopting Virus-like Features for Enhanced Immune Potentiation

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

Given the privilege of nanocarriers in lymphatic transport, nanoparticles have been shown to enhance the delivery of target antigens to lymph nodes and resident immune cells for processing and immune activation. In the aforementioned study on polypropylene sulfide particles, for instance, Reddy et al. demonstrated increased resident dendritic cell activation in the lymph node by ovalbumin-conjugated nanoparticles. In their animal study, strong anti-ovalbumin humoral response was observed [13] , highlighting the benefit of nanoparticle-mediated lymph node delivery on enhancing antigen processing. Moon et al. also showed nanoparticle vaccines can promote preferential accumulation of antigens in the draining lymph nodes and enhance expansion of antigen-specific T cells. Using interbilayer-crosslinked multilamellar vesicles (ICMVs), a lipid-based nanoformulation consisting of multiple layers of lipid vesicles interconnected via thiol chemistry, the investigators demonstrated enhanced antigen delivery to total DCs, macrophages and plasmacytoid DCs in the lymph nodes [50] . Interestingly, liposomes of comparable sizes were much less effective in shuttling antigens to draining lymph nodes in the same study. This observation highlighted the importance of nanoparticle stability in vaccine design as the ICMVs were more colloidally stable than liposomes. ICMV-mediated antigen delivery resulted in significantly higher humoral and cellular responses as compared to the free antigens and the liposomal formulations. The effect of nanoparticle carrier on antigen transport was also shown in a study by Chen et al., who demonstrated effective vaccination against coronaviruses using gold nanoparticle-adsorbed viral antigens. These antigen-coated nanoparticles were structurally analogous to coronaviruses in terms of size and antigen display. Immunofluorescence quantification showed that viral spike proteins delivered with 100 nm gold nanoparticles increased lymph node delivery by approximately 6-fold compared to free spike proteins. These virus-like particles showed high immunogenicity in both murine and avian models and enhanced anti-viral IgA and IgG titers and cellular immune responses in comparison to free protein antigens and a commercial WIV vaccine [155] .