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

2022; Frontiers Media; Volume: 13; Linguagem: Inglês

10.3389/fimmu.2022.1023255

1664-3224

Pedro J. Alcolea, Jaime Larraga, Daniel Rodríguez-Martín, Ana Alonso, Francisco J. Loayza, José M. Rojas, Silvia Ruiz-García, Andrés Louloudes-Lázaro, Ana B. Carlón, Pedro J. Sánchez‐Cordón, Pablo Nogales-Altozano, Natalia Redondo, Miguel Manzano, Daniel Lozano, Jesús Palomero, María Montoya, Maria Vallet‐Regí, Verónica Martı́n, Noemı́ Sevilla, Vicente Larraga,

Viral gastroenteritis research and epidemiology

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 in vivo electroporation. The immunogen fully protected K18-hACE2 mice against a lethal dose (10 5 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.