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 / Conforti, A.; Marra, E.; Palombo, F.; Roscilli, G.; Rava, M.; Fumagalli, V.; Muzi, A.; Maffei, M.; Luberto, L.; Lione, L.; Salvatori, E.; Compagnone, M.; Pinto, E.; Pavoni, E.; Bucci, F.; Vitagliano, G.; Stoppoloni, D.; Pacello, M. L.; Cappelletti, M.; Ferrara, F. F.; D'Acunto, E.; Chiarini, V.; Arriga, R.; Nyska, A.; Di Lucia, P.; Marotta, D.; Bono, E.; Giustini, L.; Sala, E.; Perucchini, C.; Paterson, J.; Ryan, K. A.; Challis, A. -R.; Matusali, G.; Colavita, F.; Caselli, G.; Criscuolo, E.; Clementi, N.; Mancini, N.; Gross, R.; Seidel, A.; Wettstein, L.; Munch, J.; Donnici, L.; Conti, M.; De Francesco, R.; Kuka, M.; Ciliberto, G.; Castilletti, C.; Capobianchi, M. R.; Ippolito, G.; Guidotti, L. G.; Rovati, L.; Iannacone, M.; Aurisicchio, L.. - In: MOLECULAR THERAPY. - ISSN 1525-0016. - 30:1(2021), pp. 311-326. [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

Fumagalli V.
;
Sala E.;Criscuolo E.;Clementi N.;Mancini N.;Kuka M.;Guidotti L. G.;Iannacone M.
Penultimo
;
2021-01-01

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.
2021
animal models
antiviral immunity
DNA vaccine
protection
SARS-CoV-2
Animals
Antibodies, Neutralizing
Antibodies, Viral
COVID-19
COVID-19 Vaccines
Female
Ferrets
Humans
Immunization
Mice
Mice, Inbred BALB C
Mice, Inbred C57BL
Mice, Transgenic
Protein Domains
Rats, Sprague-Dawley
SARS-CoV-2
Spike Glycoprotein, Coronavirus
Vaccines, DNA
Models, Animal
File in questo prodotto:
Non ci sono file associati a questo prodotto.

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/20.500.11768/133852
Citazioni
  • ???jsp.display-item.citation.pmc??? 32
  • Scopus 39
  • ???jsp.display-item.citation.isi??? 37
social impact