1. Non-replicative antibiotic resistance-free DNA vaccine encoding S and N proteins induces full protection in mice against SARS-CoV-2
- Author
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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 Martín, Noemí Sevilla, and Vicente Larraga
- Subjects
SARS-CoV-2 ,DNA vaccine ,S protein ,N protein ,mouse model ,pPAL ,Immunologic diseases. Allergy ,RC581-607 - Abstract
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 (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.
- Published
- 2022
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