DNA vaccination induced protective immunity against SARS CoV-2 infection in hamsterss

PLoS Negl Trop Dis. 2021 May 27;15(5):e0009374. doi: 10.1371/journal.pntd.0009374. eCollection 2021 May.

Abstract

The development of efficient vaccines against COVID-19 is an emergent need for global public health. The spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a major target for the COVID-19 vaccine. To quickly respond to the outbreak of the SARS-CoV-2 pandemic, a nucleic acid-based vaccine is a novel option, beyond the traditional inactivated virus vaccine or recombinant protein vaccine. Here, we report a DNA vaccine containing the spike gene for delivery via electroporation. The spike genes of SARS-CoV and SARS-CoV-2 were codon optimized for mammalian cell expression and then cloned into mammalian cell expression vectors, called pSARS-S and pSARS2-S, respectively. Spike protein expression was confirmed by immunoblotting after transient expression in HEK293T cells. After immunization, sera were collected for antigen-specific antibody and neutralizing antibody titer analyses. We found that both pSARS-S and pSARS2-S immunization induced similar levels of antibodies against S2 of SARS-CoV-2. In contrast, only pSARS2-S immunization induced antibodies against the receptor-binding domain of SARS-CoV-2. We further found that pSARS2-S immunization, but not pSARS-S immunization, could induce very high titers of neutralizing antibodies against SARS-CoV-2. We further analyzed SARS-CoV-2 S protein-specific T cell responses and found that the immune responses were biased toward Th1. Importantly, pSARS2-S immunization in hamsters could induce protective immunity against SARS-CoV-2 challenge in vivo. These data suggest that DNA vaccination could be a promising approach for protecting against COVID-19.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • COVID-19 / prevention & control*
  • Chlorocebus aethiops
  • Cricetinae
  • Electroporation
  • HEK293 Cells
  • Humans
  • Mesocricetus
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Plasmids
  • SARS-CoV-2 / genetics
  • SARS-CoV-2 / immunology*
  • Spike Glycoprotein, Coronavirus / genetics
  • Spike Glycoprotein, Coronavirus / immunology*
  • Vaccines, DNA / immunology
  • Vaccines, DNA / standards*
  • Vero Cells

Substances

  • Spike Glycoprotein, Coronavirus
  • Vaccines, DNA
  • spike protein, SARS-CoV-2

Grants and funding

This study was funded by the Ministry of Health and Welfare to LCL (No. MOHW-109-TDU-C222-000010) and the National Health Research Institutes to LSJ (No. IV-108-GP-02, IV-108-GP-03, IV-108-GP-05) of Taiwan. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.