COVID-eVax, an electroporated plasmid DNA vaccine candidate encoding the SARS-CoV-2 Receptor Binding Domain, elicits protective immune responses in animal models of COVID-19

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

The COVID-19 pandemic caused by the β-coronavirus SARS-CoV-2 has made the development of safe and effective vaccines a critical global priority. To date, four vaccines have already 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, a technology previously utilized for cancer vaccines. 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 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 significantly 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 in Italy.