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Xu Z, Wise MC, Chokkalingam N, et al. In Vivo Assembly of Nanoparticles Achieved through Synergy of Structure-Based Protein Engineering and Synthetic DNA Generates Enhanced Adaptive Immunity. Adv Sci (Weinh). 2020;7(8):1902802doi: 10.1002/advs.201902802.
Xu, Z., Wise, M. C., Chokkalingam, N., Walker, S., Tello-Ruiz, E., Elliott, S. T. C., Perales-Puchalt, A., Xiao, P., Zhu, X., Pumroy, R. A., Fisher, P. D., Schultheis, K., Schade, E., Menis, S., Guzman, S., Andersen, H., Broderick, K. E., Humeau, L. M., Muthumani, K., Moiseenkova-Bell, V., Schief, W. R., Weiner, D. B., & Kulp, D. W. (2020). In Vivo Assembly of Nanoparticles Achieved through Synergy of Structure-Based Protein Engineering and Synthetic DNA Generates Enhanced Adaptive Immunity. Advanced science (Weinheim, Baden-Wurttemberg, Germany), 7(8), 1902802. https://doi.org/10.1002/advs.201902802
Xu, Ziyang, et al. "In Vivo Assembly of Nanoparticles Achieved through Synergy of Structure-Based Protein Engineering and Synthetic DNA Generates Enhanced Adaptive Immunity." Advanced science (Weinheim, Baden-Wurttemberg, Germany) vol. 7,8 (2020): 1902802. doi: https://doi.org/10.1002/advs.201902802
Xu Z, Wise MC, Chokkalingam N, Walker S, Tello-Ruiz E, Elliott STC, Perales-Puchalt A, Xiao P, Zhu X, Pumroy RA, Fisher PD, Schultheis K, Schade E, Menis S, Guzman S, Andersen H, Broderick KE, Humeau LM, Muthumani K, Moiseenkova-Bell V, Schief WR, Weiner DB, Kulp DW. In Vivo Assembly of Nanoparticles Achieved through Synergy of Structure-Based Protein Engineering and Synthetic DNA Generates Enhanced Adaptive Immunity. Adv Sci (Weinh). 2020 Feb 27;7(8):1902802. doi: 10.1002/advs.201902802. eCollection 2020 Apr. PMID: 32328416; PMCID: PMC7175333.
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Adv Sci (Weinh). 2020 Feb 27;7(8):1902802. doi: 10.1002/advs.201902802. eCollection 2020 Apr.

In Vivo Assembly of Nanoparticles Achieved through Synergy of Structure-Based Protein Engineering and Synthetic DNA Generates Enhanced Adaptive Immunity.

Advanced science (Weinheim, Baden-Wurttemberg, Germany)

Ziyang Xu, Megan C Wise, Neethu Chokkalingam, Susanne Walker, Edgar Tello-Ruiz, Sarah T C Elliott, Alfredo Perales-Puchalt, Peng Xiao, Xizhou Zhu, Ruth A Pumroy, Paul D Fisher, Katherine Schultheis, Eric Schade, Sergey Menis, Stacy Guzman, Hanne Andersen, Kate E Broderick, Laurent M Humeau, Kar Muthumani, Vera Moiseenkova-Bell, William R Schief, David B Weiner, Daniel W Kulp

Affiliations

  1. The Vaccine and Immunotherapy Center The Wistar Institute Philadelphia PA 19104 USA.
  2. Department of Pharmacology Perelman School of Medicine University of Pennsylvania Philadelphia PA 19104 USA.
  3. Inovio Pharmaceuticals Plymouth Meeting Philadelphia PA 19422 USA.
  4. Department of Immunology and Microbiology The Scripps Research Institute La Jolla CA 92037 USA.
  5. IAVI Neutralizing Antibody Center The Scripps Research Institute La Jolla CA 92037 USA.
  6. Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery The Scripps Research Institute La Jolla CA 92037 USA.
  7. Bioqual Rockville MD 20852 USA.
  8. Ragon Institute of MGH MIT and Harvard Cambridge MA 02139 USA.
  9. Department of Microbiology Perelman School of Medicine University of Pennsylvania Philadelphia PA 19104 USA.

PMID: 32328416 PMCID: PMC7175333 DOI: 10.1002/advs.201902802

Abstract

Nanotechnologies are considered to be of growing importance to the vaccine field. Through decoration of immunogens on multivalent nanoparticles, designed nanovaccines can elicit improved humoral immunity. However, significant practical and monetary challenges in large-scale production of nanovaccines have impeded their widespread clinical translation. Here, an alternative approach is illustrated integrating computational protein modeling and adaptive electroporation-mediated synthetic DNA delivery, thus enabling direct in vivo production of nanovaccines. DNA-launched nanoparticles are demonstrated displaying an HIV immunogen spontaneously self-assembled in vivo. DNA-launched nanovaccines induce stronger humoral responses than their monomeric counterparts in both mice and guinea pigs, and uniquely elicit CD8+ effector T-cell immunity as compared to recombinant protein nanovaccines. Improvements in vaccine responses recapitulate when DNA-launched nanovaccines with alternative scaffolds and decorated antigen are designed and evaluated. Finally, evaluation of functional immune responses induced by DLnanovaccines demonstrates that, in comparison to control mice or mice immunized with DNA-encoded hemagglutinin monomer, mice immunized with a DNA-launched hemagglutinin nanoparticle vaccine fully survive a lethal influenza challenge, and have substantially lower viral load, weight loss, and influenza-induced lung pathology. Additional study of these next-generation in vivo-produced nanovaccines may offer advantages for immunization against multiple disease targets.

© 2020 The Authors. Published by WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim.

Keywords: DNA vaccines; in vivo self‐assembly; infectious diseases; nanoparticle vaccines; protein engineering

Conflict of interest statement

Z.X., D.B.W., and D.W.K. have a pending patent US.62784318. M.C.W., P.D.F., K.S., E.S., K.E.B., and L.M.H. are employees of Inovio Pharmaceuticals and as such receive salary and benefits including own

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