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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dc.contributor.authorAlcolea Alcolea, Pedro José
dc.contributor.authorLarraga, Jaime
dc.contributor.authorRodríguez-Martín, Daniel
dc.contributor.authorAlonso, Ana
dc.contributor.authorLoayza, Francisco
dc.contributor.authorRojas, José M.
dc.contributor.authorRuiz García, Silvia
dc.contributor.authorLouloudes Lázaro, Andrés
dc.contributor.authorCarlón, Ana B.
dc.contributor.authorSánchez Cordón, Pedro José
dc.contributor.authorNogales Altozano, Pablo
dc.contributor.authorRedondo, Natalia
dc.contributor.authorManzano García, Miguel
dc.contributor.authorLozano Borregón, Daniel
dc.contributor.authorPalomero, Jesús
dc.contributor.authorMontoya, María
dc.contributor.authorVallet Regí, María Dulce Nombre
dc.contributor.authorMartín García, Verónica
dc.contributor.authorSevilla, Noemí
dc.contributor.authorLarraga, Vicente
dc.date.accessioned2023-06-22T13:00:57Z
dc.date.available2023-06-22T13:00:57Z
dc.date.issued2022-11-09
dc.description.abstractSARS-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.
dc.description.departmentDepto. de Química en Ciencias Farmacéuticas
dc.description.facultyFac. de Farmacia
dc.description.refereedTRUE
dc.description.sponsorshipPTI-Salud Global (CSIC)
dc.description.sponsorshipCenter for Technological and Industrial Development (CDTI)
dc.description.sponsorshipREACT-ANTICIPA-UCM (Comunidad de Madrid)
dc.description.sponsorshipEuropean Research Council (Advanced Grant VERDI, ERC2015AdG grant number 694160)
dc.description.statuspub
dc.eprint.idhttps://eprints.ucm.es/id/eprint/77978
dc.identifier.doi10.3389/fimmu.2022.1023255
dc.identifier.issn1664-3224
dc.identifier.officialurlhttps://www.frontiersin.org/journals/immunology
dc.identifier.urihttps://hdl.handle.net/20.500.14352/73418
dc.journal.titleFrontiers in Immunology
dc.language.isoeng
dc.publisherFrontiers Media
dc.relation.projectIDAdvanced Grant VERDI, ERC2015AdG grant number 694160
dc.rightsAtribución 3.0 España
dc.rights.accessRightsopen access
dc.rights.urihttps://creativecommons.org/licenses/by/3.0/es/
dc.subject.cdu615.46
dc.subject.cdu615.371
dc.subject.cdu578.834
dc.subject.cdu546
dc.subject.keywordSARS-CoV-2
dc.subject.keywordDNA vaccine
dc.subject.keywordS protein
dc.subject.keywordN protein
dc.subject.keywordMouse model
dc.subject.keywordpPAL
dc.subject.keywordFurin
dc.subject.ucmInmunología
dc.subject.ucmQuímica inorgánica (Farmacia)
dc.subject.ucmTecnología farmaceútica
dc.subject.unesco2412 Inmunología
dc.titleNon-replicative antibiotic resistance-free DNA vaccine encoding S and N proteins induces full protection in mice against SARS-CoV-2
dc.typejournal article
dc.volume.number13
dspace.entity.typePublication
relation.isAuthorOfPublication2a7febe9-6dd2-4117-aa12-552e54c12bd3
relation.isAuthorOfPublicationbf1fb240-43ed-4474-8dc0-2491074f4ad3
relation.isAuthorOfPublication791023b8-2531-44eb-ba01-56e3b7caa0cb
relation.isAuthorOfPublication.latestForDiscovery2a7febe9-6dd2-4117-aa12-552e54c12bd3
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