COVID-eVax, an electroporated DNA vaccine candidate encoding the SARS-CoV-2 RBD, elicits protective responses in animal models.
Mol Ther
; 30(1): 311-326, 2022 01 05.
Article
in English
| MEDLINE | ID: covidwho-1450246
ABSTRACT
The COVID-19 pandemic caused by SARS-CoV-2 has made the development of safe and effective vaccines a critical priority. To date, four vaccines have been approved by European and American authorities for preventing COVID-19, but the development of additional vaccine platforms with improved supply and logistics profiles remains a pressing need. Here we report the preclinical evaluation of a novel COVID-19 vaccine candidate based on the electroporation of engineered, synthetic cDNA encoding a viral antigen in the skeletal muscle. We constructed a set of prototype DNA vaccines expressing various forms of the SARS-CoV-2 spike (S) protein and assessed their immunogenicity in animal models. Among them, COVID-eVax-a DNA plasmid encoding a secreted monomeric form of SARS-CoV-2 S protein receptor-binding domain (RBD)-induced the most potent anti-SARS-CoV-2 neutralizing antibody responses (including against the current most common variants of concern) and a robust T cell response. Upon challenge with SARS-CoV-2, immunized K18-hACE2 transgenic mice showed reduced weight loss, improved pulmonary function, and lower viral replication in the lungs and brain. COVID-eVax conferred significant protection to ferrets upon SARS-CoV-2 challenge. In summary, this study identifies COVID-eVax as an ideal COVID-19 vaccine candidate suitable for clinical development. Accordingly, a combined phase I-II trial has recently started.
Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Immunization
/
Vaccines, DNA
/
Models, Animal
/
Spike Glycoprotein, Coronavirus
/
COVID-19 Vaccines
/
SARS-CoV-2
/
COVID-19
Type of study:
Experimental Studies
/
Prognostic study
/
Randomized controlled trials
Topics:
Vaccines
/
Variants
Limits:
Animals
/
Female
/
Humans
Language:
English
Journal:
Mol Ther
Journal subject:
Molecular Biology
/
Therapeutics
Year:
2022
Document Type:
Article
Affiliation country:
J.ymthe.2021.09.011
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