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.

COVID-eVax, an electroporated DNA vaccine candidate encoding the SARS-CoV-2 RBD, elicits protective responses in animal models / A. Conforti, E. Marra, F. Palombo, G. Roscilli, M. Ravà, V. Fumagalli, A. Muzi, M. Maffei, L. Luberto, L. Lione, E. Salvatori, M. Compagnone, E. Pinto, E. Pavoni, F. Bucci, G. Vitagliano, D. Stoppoloni, M.L. Pacello, M. Cappelletti, F.F. Ferrara, E. D'Acunto, V. Chiarini, R. Arriga, A. Nyska, P. Di Lucia, D. Marotta, E. Bono, L. Giustini, E. Sala, C. Perucchini, J. Paterson, K.A. Ryan, A. Challis, G. Matusali, F. Colavita, G. Caselli, E. Criscuolo, N. Clementi, N. Mancini, R. Groß, A. Seidel, L. Wettstein, J. Münch, L. Donnici, M. Conti, R. De Francesco, M. Kuka, G. Ciliberto, C. Castilletti, M.R. Capobianchi, G. Ippolito, L.G. Guidotti, L. Rovati, M. Iannacone, L. Aurisicchio. - In: MOLECULAR THERAPY. - ISSN 1525-0016. - 29:12(2021 Dec), pp. 1-16. [10.1016/j.ymthe.2021.09.011]

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

V. Fumagalli
Membro del Collaboration Group
;
L. Donnici
Membro del Collaboration Group
;
M. Conti
Membro del Collaboration Group
;
R. De Francesco
Supervision
;
2021

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.
DNA vaccine; SARS-CoV-2; animal models; antiviral immunity; protection
Settore BIO/19 - Microbiologia Generale
20-set-2021
Article (author)
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/871585
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