Modulation of lipid nanoparticle-formulated plasmid DNA drives innate immune activation promoting adaptive immunity
Nicholas J. Tursi, Sachchidanand Tiwari, Nicole M. Bedanova, Toshitha Kannan, Elizabeth M. Parzych, Nisreen M.A. Okba, Kevin Liaw, András Sárközy, Cory Livingston, Maria Ibanez Trullen, E. Gary, Máté Vadovics, Niklas Laenger, Jennifer Londregan, M. S. A. Alam Khan, Serena Omo-Lamai, Hiromi Muramatsu, Kerry Blatney, Casey E. Hojecki, Viviane Machado, Igor Maricic, Trevor R. F. Smith, Laurent Humeau, Ami Patel, Andrew V. Kossenkov, Jacob S. Brenner, David Allman, Florian Krammer, Norbert Pardi, David B. Weiner
Abstract
T cell responses relative to mRNA-LNPs or adjuvanted protein, with memory responses persisting beyond one year. In rabbits immunized with HA DNA-LNP, we observed immune responses comparable or superior to mRNA-LNPs at the same dose. In an additional model, a SARS-CoV-2 spike-encoding DNA-LNP elicited protective efficacy comparable to spike mRNA-LNPs. Our study identifies a platform-specific priming mechanism for DNA-LNPs divergent from mRNA-LNPs or adjuvanted protein, suggesting avenues for this approach in prophylactic and therapeutic vaccine development.