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

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...

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Main Authors: 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
Format: Article
Language:English
Published: Elsevier 2024-03-01
Series:Molecular Therapy: Methods & Clinical Development
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2329050123002085
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author 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
author_facet 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
author_sort Hung-Chun Liao
collection DOAJ
description 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.
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spelling doaj.art-2187e81bfaf341bcb83a79cad68ec35c2023-12-19T04:17:07ZengElsevierMolecular Therapy: Methods & Clinical Development2329-05012024-03-01321101169Lipid nanoparticle-encapsulated DNA vaccine robustly induce superior immune responses to the mRNA vaccine in Syrian hamstersHung-Chun Liao0Kuan-Yin Shen1Chung-Hsiang Yang2Fang-Feng Chiu3Chen-Yi Chiang4Kit Man Chai5Wan-Chun Huang6Hui-Min Ho7Yi-Hua Chen8Min-Syuan Huang9Ching-Len Liao10Hsin-Wei Chen11Ming-Hsi Huang12Shih-Jen Liu13National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Miaoli, TaiwanNational Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Miaoli, TaiwanNational Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Miaoli, TaiwanNational Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Miaoli, TaiwanNational Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Miaoli, TaiwanNational Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Miaoli, TaiwanNational Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Miaoli, TaiwanNational Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Miaoli, TaiwanNational Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Miaoli, TaiwanNational Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Miaoli, TaiwanNational Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Miaoli, TaiwanNational Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Miaoli, Taiwan; Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan; Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, TaiwanNational Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Miaoli, Taiwan; Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan; Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Corresponding author: Ming-Hsi Huang, National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Miaoli, Taiwan.National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Miaoli, Taiwan; Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan; Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Corresponding author: Shih-Jen Liu, National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Miaoli, Taiwan.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.http://www.sciencedirect.com/science/article/pii/S2329050123002085lipid nanoparticlemRNA vaccineDNA vaccineDNA deliverySARS-CoV-2
spellingShingle 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
Lipid nanoparticle-encapsulated DNA vaccine robustly induce superior immune responses to the mRNA vaccine in Syrian hamsters
Molecular Therapy: Methods & Clinical Development
lipid nanoparticle
mRNA vaccine
DNA vaccine
DNA delivery
SARS-CoV-2
title Lipid nanoparticle-encapsulated DNA vaccine robustly induce superior immune responses to the mRNA vaccine in Syrian hamsters
title_full Lipid nanoparticle-encapsulated DNA vaccine robustly induce superior immune responses to the mRNA vaccine in Syrian hamsters
title_fullStr Lipid nanoparticle-encapsulated DNA vaccine robustly induce superior immune responses to the mRNA vaccine in Syrian hamsters
title_full_unstemmed Lipid nanoparticle-encapsulated DNA vaccine robustly induce superior immune responses to the mRNA vaccine in Syrian hamsters
title_short Lipid nanoparticle-encapsulated DNA vaccine robustly induce superior immune responses to the mRNA vaccine in Syrian hamsters
title_sort lipid nanoparticle encapsulated dna vaccine robustly induce superior immune responses to the mrna vaccine in syrian hamsters
topic lipid nanoparticle
mRNA vaccine
DNA vaccine
DNA delivery
SARS-CoV-2
url http://www.sciencedirect.com/science/article/pii/S2329050123002085
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