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Frontiers in Immunology
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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

Authors: Alcolea Alcolea, Pedro José; Larraga, Jaime; Rodríguez-Martín, Daniel; Alonso, Ana; Loayza, Francisco; Rojas, José M.; Ruiz García, Silvia; +13 Authors

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

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.

Country
Spain
Keywords

DNA vaccine, 2412 Inmunología, COVID-19 Vaccines, mouse model, ADN, Immunology, Inmunología, furina, N protein, Mouse model, 615.371, S protein, Tecnología farmaceútica, Mice, pPAL, 615.46, Vaccines, DNA, Animals, Humans, 3209 Farmacolog?a, 578.834, Pandemics, Furin, Mammals, Mice, Inbred BALB C, SARS-CoV-2, virus del SRAS, COVID-19, Viral Vaccines, DNA, 546, RC581-607, SARS Virus, Química inorgánica (Farmacia), Anti-Bacterial Agents, Mice, Inbred C57BL, 3209 Farmacología, Immunologic diseases. Allergy, 6310.03 Enfermedad, furin

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    popularity
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    Top 10%
    influence
    This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
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    This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
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selected citations
These citations are derived from selected sources.
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
10
Top 10%
Average
Top 10%
Green
gold