A universal SARS-CoV DNA vaccine inducing highly cross-reactive neutralizing antibodies and T cells.
Angiotensin-Converting Enzyme 2
/ genetics
Animals
Antibodies, Neutralizing
Antibodies, Viral
COVID-19
/ prevention & control
COVID-19 Vaccines
Humans
Mice
Nucleoproteins
SARS-CoV-2
Spike Glycoprotein, Coronavirus
/ genetics
T-Lymphocytes
Vaccines, DNA
/ genetics
Viral Envelope Proteins
/ chemistry
Viral Vaccines
/ genetics
DNA vaccine
SARS-CoV-2
in vivo electroporation
preclinical development
universal SARS vaccine
Journal
EMBO molecular medicine
ISSN: 1757-4684
Titre abrégé: EMBO Mol Med
Pays: England
ID NLM: 101487380
Informations de publication
Date de publication:
10 10 2022
10 10 2022
Historique:
revised:
16
08
2022
received:
04
02
2022
accepted:
17
08
2022
pubmed:
21
8
2022
medline:
12
10
2022
entrez:
20
8
2022
Statut:
ppublish
Résumé
New variants in the SARS-CoV-2 pandemic are more contagious (Alpha/Delta), evade neutralizing antibodies (Beta), or both (Omicron). This poses a challenge in vaccine development according to WHO. We designed a more universal SARS-CoV-2 DNA vaccine containing receptor-binding domain loops from the huCoV-19/WH01, the Alpha, and the Beta variants, combined with the membrane and nucleoproteins. The vaccine induced spike antibodies crossreactive between huCoV-19/WH01, Beta, and Delta spike proteins that neutralized huCoV-19/WH01, Beta, Delta, and Omicron virus in vitro. The vaccine primed nucleoprotein-specific T cells, unlike spike-specific T cells, recognized Bat-CoV sequences. The vaccine protected mice carrying the human ACE2 receptor against lethal infection with the SARS-CoV-2 Beta variant. Interestingly, priming of cross-reactive nucleoprotein-specific T cells alone was 60% protective, verifying observations from humans that T cells protect against lethal disease. This SARS-CoV vaccine induces a uniquely broad and functional immunity that adds to currently used vaccines.
Identifiants
pubmed: 35986481
doi: 10.15252/emmm.202215821
pmc: PMC9538582
doi:
Substances chimiques
Antibodies, Neutralizing
0
Antibodies, Viral
0
COVID-19 Vaccines
0
Nucleoproteins
0
Spike Glycoprotein, Coronavirus
0
Vaccines, DNA
0
Viral Envelope Proteins
0
Viral Vaccines
0
spike protein, SARS-CoV-2
0
Angiotensin-Converting Enzyme 2
EC 3.4.17.23
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e15821Informations de copyright
© 2022 The Authors. Published under the terms of the CC BY 4.0 license.
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