Frontiers in Immunology (Nov 2022)

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

  • 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,
  • Vicente Larraga

DOI
https://doi.org/10.3389/fimmu.2022.1023255
Journal volume & issue
Vol. 13

Abstract

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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.

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