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...
Main Authors: | , , , , , , , , , , , , , |
---|---|
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 |
_version_ | 1827580145633853440 |
---|---|
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. |
first_indexed | 2024-03-08T22:13:57Z |
format | Article |
id | doaj.art-2187e81bfaf341bcb83a79cad68ec35c |
institution | Directory Open Access Journal |
issn | 2329-0501 |
language | English |
last_indexed | 2024-03-08T22:13:57Z |
publishDate | 2024-03-01 |
publisher | Elsevier |
record_format | Article |
series | Molecular Therapy: Methods & Clinical Development |
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 |
work_keys_str_mv | AT hungchunliao lipidnanoparticleencapsulateddnavaccinerobustlyinducesuperiorimmuneresponsestothemrnavaccineinsyrianhamsters AT kuanyinshen lipidnanoparticleencapsulateddnavaccinerobustlyinducesuperiorimmuneresponsestothemrnavaccineinsyrianhamsters AT chunghsiangyang lipidnanoparticleencapsulateddnavaccinerobustlyinducesuperiorimmuneresponsestothemrnavaccineinsyrianhamsters AT fangfengchiu lipidnanoparticleencapsulateddnavaccinerobustlyinducesuperiorimmuneresponsestothemrnavaccineinsyrianhamsters AT chenyichiang lipidnanoparticleencapsulateddnavaccinerobustlyinducesuperiorimmuneresponsestothemrnavaccineinsyrianhamsters AT kitmanchai lipidnanoparticleencapsulateddnavaccinerobustlyinducesuperiorimmuneresponsestothemrnavaccineinsyrianhamsters AT wanchunhuang lipidnanoparticleencapsulateddnavaccinerobustlyinducesuperiorimmuneresponsestothemrnavaccineinsyrianhamsters AT huiminho lipidnanoparticleencapsulateddnavaccinerobustlyinducesuperiorimmuneresponsestothemrnavaccineinsyrianhamsters AT yihuachen lipidnanoparticleencapsulateddnavaccinerobustlyinducesuperiorimmuneresponsestothemrnavaccineinsyrianhamsters AT minsyuanhuang lipidnanoparticleencapsulateddnavaccinerobustlyinducesuperiorimmuneresponsestothemrnavaccineinsyrianhamsters AT chinglenliao lipidnanoparticleencapsulateddnavaccinerobustlyinducesuperiorimmuneresponsestothemrnavaccineinsyrianhamsters AT hsinweichen lipidnanoparticleencapsulateddnavaccinerobustlyinducesuperiorimmuneresponsestothemrnavaccineinsyrianhamsters AT minghsihuang lipidnanoparticleencapsulateddnavaccinerobustlyinducesuperiorimmuneresponsestothemrnavaccineinsyrianhamsters AT shihjenliu lipidnanoparticleencapsulateddnavaccinerobustlyinducesuperiorimmuneresponsestothemrnavaccineinsyrianhamsters |