Non-replicative antibiotic resistance-free DNA vaccine encoding S and N proteins induces full protection in mice against SARS-CoV-2

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Alcolea Alcolea, Pedro José and Larraga, Jaime and Rodríguez-Martín, Daniel and Alonso, Ana and Loayza, Francisco and Rojas, José M. and Ruiz García, Silvia and Louloudes Lázaro, Andrés and Carlón, Ana B. and Sánchez Cordón, Pedro José and Nogales Altozano, Pablo and Redondo, Natalia and Manzano García, Miguel and Lozano Borregón, Daniel and Palomero, Jesús and Montoya, María and Vallet Regí, María and Martín García, Verónica and Sevilla, Noemí and Larraga, Vicente (2022) Non-replicative antibiotic resistance-free DNA vaccine encoding S and N proteins induces full protection in mice against SARS-CoV-2. Frontiers in Immunology, 13 . ISSN 1664-3224

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Official URL: https://www.frontiersin.org/journals/immunology



Abstract

SARS-CoV-2 vaccines currently in use have contributed to controlling the COVID-19 pandemic. Notwithstanding, the high mutation rate, fundamentally in the spike glycoprotein (S), is causing the emergence of new variants. Solely
utilizing this antigen is a drawback that may reduce the efficacy of these vaccines. Herein we pre ent a DNA vaccine candidate that contains the genes encoding the S and the nucleocapsid (N) proteins implemented into the nonreplicative mammalian expression plasmid vector, pPAL. This plasmid lacks antibiotic resistance genes and contains an alternative selectable marker for
production. The S gene sequence was modified to avoid furin cleavage (Sfs). Potent humoral and cellular immune responses were observed in C57BL/6J mice vaccinated with pPAL-Sfs + pPAL-N following a prime/boost regimen by the intramuscular route applying in vivo electroporation. The immunogen fully protected K18-hACE2 mice against a lethal dose (105 PFU) of SARS-CoV-2. Viral replication was completely controlled in the lungs, brain, and heart of vaccinated mice. Therefore, pPAL-Sfs + pPAL-N is a promising DNA vaccine candidate for protection from COVID-19.


Item Type:Article
Uncontrolled Keywords:SARS-CoV-2; DNA vaccine; S protein; N protein; Mouse model; pPAL; Furin
Subjects:Medical sciences > Medicine > Immunology
Medical sciences > Pharmacy > Inorganic chemistry
Medical sciences > Pharmacy > Pharmaceutical technology
ID Code:77978
Deposited On:05 May 2023 09:12
Last Modified:05 May 2023 09:12

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