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.
Highlights
The emerging infectious disease COVID-19, caused by severe acute respiratory syndromeassociated coronavirus 2 (SARS-CoV-2), has had significant economic impacts in countries affected by the disease outbreak in 2019–2020 [1]
We developed DNA vaccines containing the spike gene from SARS-CoV-2 and delivered via electroporation
Because the antigen expression strongly correlated to vaccine efficacy, we designed different spike protein fragments, including RBD, RBD to TM or Spike with transmembrane domain (TM) deletion, with human tissue plasminogen activation leader sequence that may increase the secretion of antigens [21]
Summary
The emerging infectious disease COVID-19, caused by severe acute respiratory syndromeassociated coronavirus 2 (SARS-CoV-2), has had significant economic impacts in countries affected by the disease outbreak in 2019–2020 [1]. Based on previous studies on SARS and MERS, S protein-based vaccines have been proven to induce neutralizing antibodies and T cell immune responses to coronaviruses and protect animals from virus challenge [4, 5]. COVID-19 vaccine candidates could be developed using inactivated virus, recombinant or synthetic viral components, recombinant virus, or viral mRNA or DNA. The latter approach is attractive because viral DNA can be produced quickly and delivered worldwide without a cold chain system. Fully synthetic DNA derived from the sequence encoding the viral protein, could induce both humoral and cell-mediated immune responses against pathogens [8, 9]
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