Alcolea Alcolea, Pedro JoséLarraga, JaimeRodríguez-Martín, DanielAlonso, AnaLoayza, FranciscoRojas, José M.Ruiz García, SilviaLouloudes Lázaro, AndrésCarlón, Ana B.Sánchez Cordón, Pedro JoséNogales Altozano, PabloRedondo, NataliaManzano García, MiguelLozano Borregón, DanielPalomero, JesúsMontoya, MaríaVallet Regí, María Dulce NombreMartín García, VerónicaSevilla, NoemíLarraga, Vicente2023-06-222023-06-222022-11-091664-322410.3389/fimmu.2022.1023255https://hdl.handle.net/20.500.14352/73418SARS-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.engAtribución 3.0 EspañaNon-replicative antibiotic resistance-free DNA vaccine encoding S and N proteins induces full protection in mice against SARS-CoV-2journal articlehttps://www.frontiersin.org/journals/immunologyopen access615.46615.371578.834546SARS-CoV-2DNA vaccineS proteinN proteinMouse modelpPALFurinInmunologíaQuímica inorgánica (Farmacia)Tecnología farmaceútica2412 Inmunología