Lipid nanoparticle-encapsulated DNA vaccine robustly induce superior immune responses to the mRNA vaccine in Syrian hamsters

• Published in: Molecular therapy. Methods & clinical development Vol. 32; no. 1; p. 101169
• Main Authors: Liao, Hung-Chun, Shen, Kuan-Yin, Yang, Chung-Hsiang, Chiu, Fang-Feng, Chiang, Chen-Yi, Chai, Kit Man, Huang, Wan-Chun, Ho, Hui-Min, Chen, Yi-Hua, Huang, Min-Syuan, Liao, Ching-Len, Chen, Hsin-Wei, Huang, Ming-Hsi, Liu, Shih-Jen
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 14.03.2024; Elsevier
• Subjects: DNA delivery; DNA vaccine; lipid nanoparticle; mRNA vaccine; SARS-CoV-2; DNA vaccine; lipid nanoparticle; SARS-CoV-2; DNA delivery; mRNA vaccine
• ISSN: 2329-0501; 2329-0501
• DOI: 10.1016/j.omtm.2023.101169

DNA vaccines for infectious diseases and cancer have been explored for years. To date, only one DNA vaccine (ZyCoV-D) has been authorized for emergency use in India. DNA vaccines are inexpensive and long-term thermostable, however, limited by the low efficiency of intracellular delivery. The recent success of mRNA/lipid nanoparticle (LNP) technology in the coronavirus disease 2019 (COVID-19) pandemic has opened a new application for nucleic acid-based vaccines. Here, we report that plasmid encoding a trimeric spike protein with LNP delivery (pTS/LNP), similar to those in Moderna’s COVID-19 vaccine, induced more effective humoral responses than naked pTS or pTS delivered via electroporation. Compared with TSmRNA/LNP, pTS/LNP immunization induced a comparable level of neutralizing antibody titers and significant T helper 1-biased immunity in mice; it also prolonged the maintenance of higher antigen-specific IgG and neutralizing antibody titers in hamsters. Importantly, pTS/LNP immunization exhibits enhanced cross-neutralizing activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants and protects hamsters from the challenge of SARS-CoV-2 (Wuhan strain and the Omicron BA.1 variant). This study indicates that pDNA/LNPs as a promising platform could be a next-generation vaccine technology. [Display omitted] Liu and colleagues introduce a DNA vaccine delivery system with easy administration using LNPs. This study highlights prolonged protein expression, robust humoral responses, and increased protection against viral challenges, including the Omicron variant. This DNA/LNP vaccine technology promises a potent alternative to current mRNA-based vaccines.