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Mol Ther Methods Clin Dev . Lipid nanoparticle-encapsulated DNA vaccine robustly induce superior immune responses to the mRNA vaccine in Syrian ham

tetano

Editor, Senior Moderator
Mol Ther Methods Clin Dev


. 2023 Dec 5;32(1):101169.
doi: 10.1016/j.omtm.2023.101169. eCollection 2024 Mar 14. Lipid nanoparticle-encapsulated DNA vaccine robustly induce superior immune responses to the mRNA vaccine in Syrian hamsters

Hung-Chun Liao[SUP] 1 [/SUP], Kuan-Yin Shen[SUP] 1 [/SUP], Chung-Hsiang Yang[SUP] 1 [/SUP], Fang-Feng Chiu[SUP] 1 [/SUP], Chen-Yi Chiang[SUP] 1 [/SUP], Kit Man Chai[SUP] 1 [/SUP], Wan-Chun Huang[SUP] 1 [/SUP], Hui-Min Ho[SUP] 1 [/SUP], Yi-Hua Chen[SUP] 1 [/SUP], Min-Syuan Huang[SUP] 1 [/SUP], Ching-Len Liao[SUP] 1 [/SUP], Hsin-Wei Chen[SUP] 1 2 3 [/SUP], Ming-Hsi Huang[SUP] 1 2 3 [/SUP], Shih-Jen Liu[SUP] 1 2 3 [/SUP]



Affiliations
Abstract

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.

Keywords: DNA delivery; DNA vaccine; SARS-CoV-2; lipid nanoparticle; mRNA vaccine.

 
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