DNA origami vaccine (DoriVac) nanoparticles improve both humoral and cellular immune responses to infectious diseases

Zeng, Y.; Young, O.; Si, L.; Ku, M. W.; Isinelli, G.; Rajwar, A.; Jiang, A.; Wintersinger, C.; Graveline, A.; Vernet, A.; Sanchez, M.; Ryu, J. H.; Kwon, I. C.; Goyal, G.; Ingber, D.; Shih, W.

doi:10.1101/2023.12.29.573647

bioRxiv · 10.1101/2023.12.29.573647

DNA origami vaccine (DoriVac) nanoparticles improve both humoral and cellular immune responses to infectious diseases

Zeng, Y.·Young, O.·Si, L.·Ku, M. W.·Isinelli, G.·Rajwar, A.·Jiang, A.·Wintersinger, C.·Graveline, A.·Vernet, A.·Sanchez, M.·Ryu, J. H.·Kwon, I. C.·Goyal, G.·Ingber, D.·Shih, W.

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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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Zeng, Y., Young, O., Si, L., Ku, M. W., Isinelli, G., Rajwar, A., Jiang, A., Wintersinger, C., Graveline, A., Vernet, A., Sanchez, M., Ryu, J. H., Kwon, I. C., Goyal, G., Ingber, D., Shih, W.. 2024-01-02. DNA origami vaccine (DoriVac) nanoparticles improve both humoral and cellular immune responses to infectious diseases. https://doi.org/10.1101/2023.12.29.573647

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