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A first-in-human trial on the safety and immunogenicity of COVID-eVax, a cellular response-skewed DNA vaccine against COVID-19

The COVID-19 pandemic and the need for additional safe, effective, and affordable vaccines gave new impetus into development of vaccine genetic platforms. Here we report the findings from the phase 1, first-in-human, dose-escalation study of COVID-eVax, a DNA vaccine encoding the receptor binding do...

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Autores principales: Aurisicchio, Luigi, Brambilla, Nadia, Cazzaniga, Marina E., Bonfanti, Paolo, Milleri, Stefano, Ascierto, Paolo A., Capici, Serena, Vitalini, Cristina, Girolami, Federica, Giacovelli, Giampaolo, Caselli, Gianfranco, Visintin, Michela, Fanti, Francesca, Ghirri, Matteo, Conforti, Antonella, Compagnone, Mirco, Lione, Lucia, Salvatori, Erika, Pinto, Eleonora, Muzi, Alessia, Marra, Emanuele, Palombo, Fabio, Roscilli, Giuseppe, Manenti, Alessandro, Montomoli, Emanuele, Cadossi, Matteo, Rovati, Lucio C.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society of Gene & Cell Therapy 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9792419/
https://www.ncbi.nlm.nih.gov/pubmed/36575794
http://dx.doi.org/10.1016/j.ymthe.2022.12.017
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author Aurisicchio, Luigi
Brambilla, Nadia
Cazzaniga, Marina E.
Bonfanti, Paolo
Milleri, Stefano
Ascierto, Paolo A.
Capici, Serena
Vitalini, Cristina
Girolami, Federica
Giacovelli, Giampaolo
Caselli, Gianfranco
Visintin, Michela
Fanti, Francesca
Ghirri, Matteo
Conforti, Antonella
Compagnone, Mirco
Lione, Lucia
Salvatori, Erika
Pinto, Eleonora
Muzi, Alessia
Marra, Emanuele
Palombo, Fabio
Roscilli, Giuseppe
Manenti, Alessandro
Montomoli, Emanuele
Cadossi, Matteo
Rovati, Lucio C.
author_facet Aurisicchio, Luigi
Brambilla, Nadia
Cazzaniga, Marina E.
Bonfanti, Paolo
Milleri, Stefano
Ascierto, Paolo A.
Capici, Serena
Vitalini, Cristina
Girolami, Federica
Giacovelli, Giampaolo
Caselli, Gianfranco
Visintin, Michela
Fanti, Francesca
Ghirri, Matteo
Conforti, Antonella
Compagnone, Mirco
Lione, Lucia
Salvatori, Erika
Pinto, Eleonora
Muzi, Alessia
Marra, Emanuele
Palombo, Fabio
Roscilli, Giuseppe
Manenti, Alessandro
Montomoli, Emanuele
Cadossi, Matteo
Rovati, Lucio C.
author_sort Aurisicchio, Luigi
collection PubMed
description The COVID-19 pandemic and the need for additional safe, effective, and affordable vaccines gave new impetus into development of vaccine genetic platforms. Here we report the findings from the phase 1, first-in-human, dose-escalation study of COVID-eVax, a DNA vaccine encoding the receptor binding domain (RBD) of the SARS-CoV-2 spike protein. Sixty-eight healthy adults received two doses of 0.5, 1, or 2 mg 28 days apart, or a single 2-mg dose, via intramuscular injection followed by electroporation, and they were monitored for 6 months. All participants completed the primary safety and immunogenicity assessments after 8 weeks. COVID-eVax was well tolerated, with mainly mild to moderate solicited adverse events (tenderness, pain, bruising, headache, and malaise/fatigue), less frequent after the second dose, and it induced an immune response (binding antibodies and/or T cells) at all prime-boost doses tested in up to 90% of the volunteers at the highest dose. However, the vaccine did not induce neutralizing antibodies, while particularly relevant was the T cell-mediated immunity, with a robust Th1 response. This T cell-skewed immunological response adds significant information to the DNA vaccine platform and should be assessed in further studies for its protective capacity and potential usefulness also in other therapeutic areas, such as oncology.
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spelling pubmed-97924192022-12-27 A first-in-human trial on the safety and immunogenicity of COVID-eVax, a cellular response-skewed DNA vaccine against COVID-19 Aurisicchio, Luigi Brambilla, Nadia Cazzaniga, Marina E. Bonfanti, Paolo Milleri, Stefano Ascierto, Paolo A. Capici, Serena Vitalini, Cristina Girolami, Federica Giacovelli, Giampaolo Caselli, Gianfranco Visintin, Michela Fanti, Francesca Ghirri, Matteo Conforti, Antonella Compagnone, Mirco Lione, Lucia Salvatori, Erika Pinto, Eleonora Muzi, Alessia Marra, Emanuele Palombo, Fabio Roscilli, Giuseppe Manenti, Alessandro Montomoli, Emanuele Cadossi, Matteo Rovati, Lucio C. Mol Ther Original Article The COVID-19 pandemic and the need for additional safe, effective, and affordable vaccines gave new impetus into development of vaccine genetic platforms. Here we report the findings from the phase 1, first-in-human, dose-escalation study of COVID-eVax, a DNA vaccine encoding the receptor binding domain (RBD) of the SARS-CoV-2 spike protein. Sixty-eight healthy adults received two doses of 0.5, 1, or 2 mg 28 days apart, or a single 2-mg dose, via intramuscular injection followed by electroporation, and they were monitored for 6 months. All participants completed the primary safety and immunogenicity assessments after 8 weeks. COVID-eVax was well tolerated, with mainly mild to moderate solicited adverse events (tenderness, pain, bruising, headache, and malaise/fatigue), less frequent after the second dose, and it induced an immune response (binding antibodies and/or T cells) at all prime-boost doses tested in up to 90% of the volunteers at the highest dose. However, the vaccine did not induce neutralizing antibodies, while particularly relevant was the T cell-mediated immunity, with a robust Th1 response. This T cell-skewed immunological response adds significant information to the DNA vaccine platform and should be assessed in further studies for its protective capacity and potential usefulness also in other therapeutic areas, such as oncology. American Society of Gene & Cell Therapy 2023-03-01 2022-12-27 /pmc/articles/PMC9792419/ /pubmed/36575794 http://dx.doi.org/10.1016/j.ymthe.2022.12.017 Text en © 2022 The American Society of Gene and Cell Therapy.
spellingShingle Original Article
Aurisicchio, Luigi
Brambilla, Nadia
Cazzaniga, Marina E.
Bonfanti, Paolo
Milleri, Stefano
Ascierto, Paolo A.
Capici, Serena
Vitalini, Cristina
Girolami, Federica
Giacovelli, Giampaolo
Caselli, Gianfranco
Visintin, Michela
Fanti, Francesca
Ghirri, Matteo
Conforti, Antonella
Compagnone, Mirco
Lione, Lucia
Salvatori, Erika
Pinto, Eleonora
Muzi, Alessia
Marra, Emanuele
Palombo, Fabio
Roscilli, Giuseppe
Manenti, Alessandro
Montomoli, Emanuele
Cadossi, Matteo
Rovati, Lucio C.
A first-in-human trial on the safety and immunogenicity of COVID-eVax, a cellular response-skewed DNA vaccine against COVID-19
title A first-in-human trial on the safety and immunogenicity of COVID-eVax, a cellular response-skewed DNA vaccine against COVID-19
title_full A first-in-human trial on the safety and immunogenicity of COVID-eVax, a cellular response-skewed DNA vaccine against COVID-19
title_fullStr A first-in-human trial on the safety and immunogenicity of COVID-eVax, a cellular response-skewed DNA vaccine against COVID-19
title_full_unstemmed A first-in-human trial on the safety and immunogenicity of COVID-eVax, a cellular response-skewed DNA vaccine against COVID-19
title_short A first-in-human trial on the safety and immunogenicity of COVID-eVax, a cellular response-skewed DNA vaccine against COVID-19
title_sort first-in-human trial on the safety and immunogenicity of covid-evax, a cellular response-skewed dna vaccine against covid-19
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9792419/
https://www.ncbi.nlm.nih.gov/pubmed/36575794
http://dx.doi.org/10.1016/j.ymthe.2022.12.017
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