DNA origami vaccine (DoriVac) nanoparticles improve both humoral and cellular immune responses to infectious diseases
Zeng, Y.; Young, O.; Xiong, Q.; Si, L.; Ku, M. W.; Bernier, S.; Dembele, H.; Isinelli, G.; Gilboa, T.; Swank, Z.; Seok, S. H.; Rajwar, A.; Jiang, A.; Zhai, Y.; Williams, L.; Hellman, C.; Wintersinger, C.; Graveline, A.; Vernet, A.; Sanchez, M.; Bardales, S.; Tomara, G.; Ryu, J. H.; Kwon, I. C.; Goyal, G.; Ingber, D.; Shih, W.
Show abstract
Current SARS-CoV-2 vaccines have demonstrated robust induction of neutralizing antibodies and CD4+ T cell activation, however CD8+ responses are variable, and the duration of immunity and protection against variants are limited. Here we repurposed our DNA origami vaccine nanotechnology, DoriVac, for targeting infectious viruses, namely SARS-CoV-2, HIV, and Ebola. The DNA origami nanoparticle, conjugated with infectious-disease-specific heptad repeat 2 (HR2) peptides, which act as highly conserved antigens, and CpG adjuvant at precise nanoscale spacing, induced neutralizing antibodies, Th1 CD4+ T cells, and CD8+ T cells in naive mice, with significant improvement over a bolus control. Pre-clinical studies using lymph-node-on-a-chip systems validated that DoriVac, when conjugated with antigenic peptides or proteins, induced promising cellular and humoral immune responses in human cells. Moreover, DoriVac bearing full-length SARS-CoV-2 spike protein achieved immune responses comparable to current mRNA vaccine platforms while potentially reducing storage constraints. These results suggest that DoriVac holds potential as a versatile, modular vaccine platform, capable of inducing both humoral and cellular immunities, underscoring its potential utility in addressing future pandemics.
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