tetano
Editor, Senior Moderator
Cell Rep Med
. 2025 Mar 13:102035.
doi: 10.1016/j.xcrm.2025.102035. Online ahead of print. Modulation of lipid nanoparticle-formulated plasmid DNA drives innate immune activation promoting adaptive immunity
Nicholas J Tursi[SUP] 1 [/SUP], Sachchidanand Tiwari[SUP] 2 [/SUP], Nicole Bedanova[SUP] 3 [/SUP], Toshitha Kannan[SUP] 3 [/SUP], Elizabeth Parzych[SUP] 3 [/SUP], Nisreen Okba[SUP] 4 [/SUP], Kevin Liaw[SUP] 3 [/SUP], András Sárközy[SUP] 2 [/SUP], Cory Livingston[SUP] 3 [/SUP], Maria Ibanez Trullen[SUP] 4 [/SUP], Ebony N Gary[SUP] 3 [/SUP], Máté Vadovics[SUP] 2 [/SUP], Niklas Laenger[SUP] 5 [/SUP], Jennifer Londregan[SUP] 6 [/SUP], Mohammad Suhail Khan[SUP] 3 [/SUP], Serena Omo-Lamai[SUP] 7 [/SUP], Hiromi Muramatsu[SUP] 2 [/SUP], Kerry Blatney[SUP] 3 [/SUP], Casey Hojecki[SUP] 3 [/SUP], Viviane Machado[SUP] 8 [/SUP], Igor Maricic[SUP] 8 [/SUP], Trevor R F Smith[SUP] 8 [/SUP], Laurent M Humeau[SUP] 8 [/SUP], Ami Patel[SUP] 3 [/SUP], Andrew Kossenkov[SUP] 3 [/SUP], Jacob S Brenner[SUP] 7 [/SUP], David Allman[SUP] 6 [/SUP], Florian Krammer[SUP] 9 [/SUP], Norbert Pardi[SUP] 10 [/SUP], David B Weiner[SUP] 11 [/SUP]
Affiliations
Nucleic acid vaccines have grown in importance over the past several years, with the development of new approaches remaining a focus. We describe a lipid nanoparticle-formulated DNA (DNA-LNP) formulation which induces robust innate and adaptive immunity with similar serological potency to mRNA-LNPs and adjuvanted protein. Using an influenza hemagglutinin (HA)-encoding construct, we show that priming with our HA DNA-LNP demonstrated stimulator of interferon genes (STING)-dependent upregulation and activation of migratory dendritic cell (DC) subpopulations. HA DNA-LNP induced superior antigen-specific CD8[SUP]+[/SUP] 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.
Keywords: DNA-LNP; T cell; adjuvanted protein; antibody; lipid nanoparticle; mRNA; plasmid DNA; vaccine.
. 2025 Mar 13:102035.
doi: 10.1016/j.xcrm.2025.102035. Online ahead of print. Modulation of lipid nanoparticle-formulated plasmid DNA drives innate immune activation promoting adaptive immunity
Nicholas J Tursi[SUP] 1 [/SUP], Sachchidanand Tiwari[SUP] 2 [/SUP], Nicole Bedanova[SUP] 3 [/SUP], Toshitha Kannan[SUP] 3 [/SUP], Elizabeth Parzych[SUP] 3 [/SUP], Nisreen Okba[SUP] 4 [/SUP], Kevin Liaw[SUP] 3 [/SUP], András Sárközy[SUP] 2 [/SUP], Cory Livingston[SUP] 3 [/SUP], Maria Ibanez Trullen[SUP] 4 [/SUP], Ebony N Gary[SUP] 3 [/SUP], Máté Vadovics[SUP] 2 [/SUP], Niklas Laenger[SUP] 5 [/SUP], Jennifer Londregan[SUP] 6 [/SUP], Mohammad Suhail Khan[SUP] 3 [/SUP], Serena Omo-Lamai[SUP] 7 [/SUP], Hiromi Muramatsu[SUP] 2 [/SUP], Kerry Blatney[SUP] 3 [/SUP], Casey Hojecki[SUP] 3 [/SUP], Viviane Machado[SUP] 8 [/SUP], Igor Maricic[SUP] 8 [/SUP], Trevor R F Smith[SUP] 8 [/SUP], Laurent M Humeau[SUP] 8 [/SUP], Ami Patel[SUP] 3 [/SUP], Andrew Kossenkov[SUP] 3 [/SUP], Jacob S Brenner[SUP] 7 [/SUP], David Allman[SUP] 6 [/SUP], Florian Krammer[SUP] 9 [/SUP], Norbert Pardi[SUP] 10 [/SUP], David B Weiner[SUP] 11 [/SUP]
Affiliations
- PMID: 40120578
- DOI: 10.1016/j.xcrm.2025.102035
Nucleic acid vaccines have grown in importance over the past several years, with the development of new approaches remaining a focus. We describe a lipid nanoparticle-formulated DNA (DNA-LNP) formulation which induces robust innate and adaptive immunity with similar serological potency to mRNA-LNPs and adjuvanted protein. Using an influenza hemagglutinin (HA)-encoding construct, we show that priming with our HA DNA-LNP demonstrated stimulator of interferon genes (STING)-dependent upregulation and activation of migratory dendritic cell (DC) subpopulations. HA DNA-LNP induced superior antigen-specific CD8[SUP]+[/SUP] 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.
Keywords: DNA-LNP; T cell; adjuvanted protein; antibody; lipid nanoparticle; mRNA; plasmid DNA; vaccine.