COVID-eVax, an electroporated DNA vaccine candidate encoding the SARS-CoV-2 RBD, elicits protective responses in animal models
Mol Ther.
2021-09;
Antonella Conforti, Emanuele Marra, Fabio Palombo, Giuseppe Roscilli, Micol Ravà, Valeria Fumagalli, Alessia Muzi, Mariano Maffei, Laura Luberto, Lucia Lione, Erika Salvatori, Mirco Compagnone, Eleonora Pinto, Emiliano Pavoni, Federica Bucci, Grazia Vitagliano, Daniela Stoppoloni, Maria Lucrezia Pacello, Manuela Cappelletti, Fabiana Fosca Ferrara, Emanuela D'Acunto, Valerio Chiarini, Roberto Arriga, Abraham Nyska, Pietro Di Lucia, Davide Marotta, Elisa Bono, Leonardo Giustini, Eleonora Sala, Chiara Perucchini, Jemma Paterson, Kathryn Ann Ryan, Amy-Rose Challis, Giulia Matusali, Francesca Colavita, Gianfranco Caselli, Elena Criscuolo, Nicola Clementi, Nicasio Mancini, Rüdiger Gro?, Alina Seidel, Lukas Wettstein, Jan Münch, Lorena Donnici, Matteo Conti, Raffaele De Francesco, Mirela Kuka, Gennaro Ciliberto, Concetta Castilletti, Maria Rosaria Capobianchi, Giuseppe Ippolito, Luca G Guidotti, Lucio Rovati, Matteo Iannacone, Luigi Aurisicchio
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| Codon Optimization |
… The synthesis and codon optimization analysis of a cDNA encoding the SARS-CoV-2 protein
S has been performed at GenScript (China). All constructs were completely synthetic and
optimized for codon usage. Codon-optimized variants took into account codon usage bias, GC … |
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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 DN... More
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.
DNA vaccine, SARS-CoV-2, animal models, antiviral immunity, protection
