| Autor: |
Matteo Iannacone, Abraham Nyska, Chiara Perucchini, Grazia Vitagliano, Davide Marotta, Rüdiger Groß, Fabio Palombo, Emanuela D’Acunto, Roberto Arriga, Valeria Fumagalli, Elena Criscuolo, Nicasio Mancini, Fabiana Fosca Ferrara, Leonardo Giustini, Elisa Bono, Erika Salvatori, Eleonora Sala, Emiliano Pavoni, Daniela Stoppoloni, Matteo Conti, Jemma Paterson, Antonella Conforti, Federica Bucci, Giuseppe Roscilli, Lukas Wettstein, Manuela Cappelletti, Luigi Aurisicchio, Lucia Lione, Jan Münch, Mirco Compagnone, Nicola Clementi, Giuseppe Ippolito, Alessia Muzi, Raffaele De Francesco, Valerio Chiarini, Maria Rosaria Capobianchi, Emanuele Marra, Alina Seidel, Amy-Rose Challis, Gianfranco Caselli, Mirela Kuka, Eleonora Pinto, Lucio C. Rovati, Luca G. Guidotti, Concetta Castilletti, Micol Ravà, Pietro Di Lucia, Mariano Maffei, Gennaro Ciliberto, Francesca Colavita, Giulia Matusali, Maria Lucrezia Pacello, Laura Luberto, Lorena Donnici, Kathryn A. Ryan |
| Rok vydání: |
2021 |
| Předmět: |
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| DOI: |
10.1101/2021.06.14.448343 |
| Popis: |
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. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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