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COVID-eVax, an electroporated DNA vaccine candidate encoding the SARS-CoV-2 RBD, elicits protective responses in animal models.


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.

SUBMITTER: Conforti A 

PROVIDER: S-EPMC8483992 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature

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COVID-eVax, an electroporated DNA vaccine candidate encoding the SARS-CoV-2 RBD, elicits protective responses in animal models.

Conforti Antonella A   Marra Emanuele E   Palombo Fabio F   Roscilli Giuseppe G   Ravà Micol M   Fumagalli Valeria V   Muzi Alessia A   Maffei Mariano M   Luberto Laura L   Lione Lucia L   Salvatori Erika E   Compagnone Mirco M   Pinto Eleonora E   Pavoni Emiliano E   Bucci Federica F   Vitagliano Grazia G   Stoppoloni Daniela D   Pacello Maria Lucrezia ML   Cappelletti Manuela M   Ferrara Fabiana Fosca FF   D'Acunto Emanuela E   Chiarini Valerio V   Arriga Roberto R   Nyska Abraham A   Di Lucia Pietro P   Marotta Davide D   Bono Elisa E   Giustini Leonardo L   Sala Eleonora E   Perucchini Chiara C   Paterson Jemma J   Ryan Kathryn Ann KA   Challis Amy-Rose AR   Matusali Giulia G   Colavita Francesca F   Caselli Gianfranco G   Criscuolo Elena E   Clementi Nicola N   Mancini Nicasio N   Groß Rüdiger R   Seidel Alina A   Wettstein Lukas L   Münch Jan J   Donnici Lorena L   Conti Matteo M   De Francesco Raffaele R   Kuka Mirela M   Ciliberto Gennaro G   Castilletti Concetta C   Capobianchi Maria Rosaria MR   Ippolito Giuseppe G   Guidotti Luca G LG   Rovati Lucio L   Iannacone Matteo M   Aurisicchio Luigi L  

Molecular therapy : the journal of the American Society of Gene Therapy 20210920 1


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  ...[more]

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