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

Hung-Chun Liao; Kuan-Yin Shen; Chung-Hsiang Yang; Fang-Feng Chiu; Chen-Yi Chiang; Kit Man Chai; Wan-Chun Huang; Hui-Min Ho; Yi-Hua Chen; Min-Syuan Huang; Ching-Len Liao; Hsin-Wei Chen; Ming-Hsi Huang; Shih-Jen Liu

doi:10.1016/j.omtm.2023.101169

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

Mol Ther Methods Clin Dev. 2023 Dec 5;32(1):101169. doi: 10.1016/j.omtm.2023.101169. eCollection 2024 Mar 14.

Authors

Hung-Chun Liao¹, Kuan-Yin Shen¹, Chung-Hsiang Yang¹, Fang-Feng Chiu¹, Chen-Yi Chiang¹, Kit Man Chai¹, Wan-Chun Huang¹, Hui-Min Ho¹, Yi-Hua Chen¹, Min-Syuan Huang¹, Ching-Len Liao¹, Hsin-Wei Chen^{1

2

3}, Ming-Hsi Huang^{1

2

3}, Shih-Jen Liu^{1

2

3}

Affiliations

¹ National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Miaoli, Taiwan.
² Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan.
³ Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.

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.