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Immunol."],"abstract":"<jats:p>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 present a DNA vaccine candidate that contains the genes encoding the S and the nucleocapsid (N) proteins implemented into the non-replicative 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 <jats:italic>in vivo<\/jats:italic> electroporation. The immunogen fully protected K18-hACE2 mice against a lethal dose (10<jats:sup>5<\/jats:sup> 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.<\/jats:p>","DOI":"10.3389\/fimmu.2022.1023255","type":"journal-article","created":{"date-parts":[[2022,11,9]],"date-time":"2022-11-09T07:07:55Z","timestamp":1667977675000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":10,"title":["Non-replicative antibiotic resistance-free DNA vaccine encoding S and N proteins induces full protection in mice against SARS-CoV-2"],"prefix":"10.3389","volume":"13","author":[{"given":"Pedro 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