DNA Based Vaccine Expressing SARS-CoV-2 Spike-CD40L Fusion Protein Confers Protection Against Challenge in a Syrian Hamster Model

Abstract

SARS-CoV-2 infections present a tremendous threat to public health. Safe and efficacious vaccines are the most effective means in preventing the infections. A variety of vaccines have demonstrated excellent efficacy and safety around the globe. Yet, development of alternative forms of vaccines remains beneficial, particularly those with simpler production processes, less stringent storage conditions, and the capability of being used in heterologous prime/boost regimens which have shown improved efficacy against many diseases. Here we reported a novel DNA vaccine comprised of the SARS-CoV-2 spike protein fused with CD40 ligand (CD40L) serving as both a targeting ligand and molecular adjuvant. A single intramuscular injection in Syrian hamsters induced significant neutralizing antibodies 3-weeks after vaccination, with a boost substantially improving immune responses. Moreover, the vaccine also reduced weight loss and suppressed viral replication in the lungs and nasal turbinates of challenged animals. Finally, the incorporation of CD40L into the DNA vaccine was shown to reduce lung pathology more effectively than the DNA vaccine devoid of CD40L. These results collectively indicate that this DNA vaccine candidate could be further explored because of its efficacy and known safety profile.

Robust and protective immune responses induced by heterologous prime‐boost vaccination with DNA‐protein dimeric RBD vaccines for COVID‐19

“…Several immunization strategies have been explored for DNA vaccine immunization. Intramuscular injection of DNA vaccine has been demonstrated to induce protective immune responses 31,50 . Furthermore, INO‐4800 is intradermally injected followed by electroporation with the CELLECTRA device.…”

“…Intramuscular injection of DNA vaccine has been demonstrated to induce protective immune responses. 31,50 Furthermore, INO-4800 is intradermally injected followed by electroporation with the CELLECTRA device. A controlled electric field is generated at the injection site to enhance the cellular uptake of the DNA plasmid.…”

Effectiveness of VSV vectored SARS-CoV-2 spike when administered through intranasal, intramuscular or a combination of both

“…Infectious viral load was quantified by plaque assay on homogenized lung and nasal turbinate tissues as previously described 24 . In brief, spin-clarified supernatants of tissue homogenates were serially diluted 1:10 in infection media (DMEM supplemented 1X non-essential amino acid, 1 mM sodium pyruvate, and 0.1% bovine serum albumin).…”

Single Immunization with Recombinant ACAM2000 Vaccinia Viruses Expressing the Spike and the Nucleocapsid Proteins Protects Hamsters against SARS-CoV-2-Caused Clinical Disease

“…Total RNA was extracted from hamster tissue samples using the RNeasy minikit (Qiagen) according to the manufacturer’s instructions. The subgenomic RNA (sgRNA) of the SARS-CoV-2 E gene was quantified with quantitative real-time PCR (qRT-PCR) using the same primer pair, probe, and standard mRNA as described previously ( 72 ). Reactions were performed in MicroAmp Fast Optical 96-well plates (Applied Biosystems) on a StepOnePlus real-time PCR machine (Applied Biosystems).…”