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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, María 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.