Preclinical evaluation of a candidate naked plasmid DNA vaccine against SARS-CoV-2

Abstract

New generation plasmid DNA vaccines may be a safe, fast and simple emergency vaccine platform for preparedness against emerging viral pathogens. Applying platform optimization strategies, we tested the pre-clinical immunogenicity and protective effect of a candidate DNA plasmid vaccine specific for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The DNA vaccine induced spike-specific binding IgG and neutralizing antibodies in mice, rabbits, and rhesus macaques together with robust Th1 dominant cellular responses in small animals. Intradermal and intramuscular needle-free administration of the DNA vaccine yielded comparable immune responses. In a vaccination-challenge study of rhesus macaques, the vaccine demonstrated protection from viral replication in the lungs following intranasal and intratracheal inoculation with SARS-CoV-2. In conclusion, the candidate plasmid DNA vaccine encoding the SARS-CoV-2 spike protein is immunogenic in different models and confers protection against lung infection in nonhuman primates. Further evaluation of this DNA vaccine candidate in clinical trials is warranted.

Neutralizing Antibodies Against the SARS-CoV-2 Omicron Variant (BA.1) 1 to 18 Weeks After the Second and Third Doses of the BNT162b2 mRNA Vaccine

“…In the latter group, given the timeframe, individuals became infected with ancestral SARS-CoV-2 strains before VOCs became dominant in Denmark. We determined 50% serum neutralization titers using a live virus microneutralization assay 5 (eAppendix in the Supplement). Paired and nonpaired numerical measurements were compared using the Wilcoxon matched-pairs signed rank test and Mann-Whitney U test, respectively.…”

Design and Immunogenicity of SARS-CoV-2 DNA vaccine encoding RBD-PVXCP fusion protein

“…After the prime/boost set of our pDNAv1 vaccine the mean RBD-specific end-point titer reached 85 712 utilizing needle-free injection method. To the best of our knowledge – we obtained the highest IgG level among all the naked pDNA vaccines that were pre-clinically tested in rabbits without non-applicable on humans electroporation 40, 49 . In order to further explore the potential of our vaccine candidate at week 6 we performed a second boost that raised the mean endpoint titer to 352 906 approaching electroporation in the prime\boost regimen.…”

“…A number of DNA-encoded vaccines were recently developed, but all of them have a common drawback of insufficient level of humoral responses in large animals 40,48,49 .…”

“…Improved delivery by electroporation and needle-free injectors (for example PharmaJet Needle-free Injection System) increased in vivo antigen expression and immune responses to DNA vaccines. Other approaches such as reduction of the size of the DNA plasmid, deletion of antibiotic resistance genes, and addition of immunostimulatory sequences into the backbone of the DNA vaccine have been shown to increase the immunogenicity of SARS-COV-2 DNA vaccine 40 .…”

SARS-CoV-2 Doggybone DNA Vaccine Produces Cross-Variant Neutralizing Antibodies and Is Protective in a COVID-19 Animal Model

“…DNA vaccines have several advantages, including stability (minimal cold-chain requirements), safety, and increased immunogenicity with administration by needle-free delivery devices [ 4 , 38 , 39 , 40 , 41 ]. However, traditional pDNA manufacture is a major bottleneck [ 42 ].…”