Synthetic SARS-CoV-2 Spike-Based DNA Vaccine Elicits Robust and Long-Lasting Th1 Humoral and Cellular Immunity in Mice

Abstract

The ongoing global pandemic of coronavirus disease 2019 (COVID-19) calls for an urgent development of effective and safe prophylactic and therapeutic measures. The spike (S) glycoprotein of severe acute respiratory syndrome-coronavirus (SARS-CoV-2) is a major immunogenic and protective protein and plays a crucial role in viral pathogenesis. In this study, we successfully constructed a synthetic codon-optimized DNA-based vaccine as a countermeasure against SARS-CoV-2, denoted VIU-1005. The design was based on a codon-optimized coding sequence of a consensus full-length S glycoprotein. The immunogenicity of the vaccine was tested in two mouse models (BALB/c and C57BL/6J). Th1-skewed systemic S-specific IgG antibodies and neutralizing antibodies (nAbs) were significantly induced in both models 4 weeks after three injections with 100 μg of the VIU-1005 vaccine via intramuscular needle injection but not intradermal or subcutaneous routes. Such immunization induced long-lasting IgG and memory T cell responses in mice that lasted for at least 6 months. Interestingly, using a needle-free system, we showed an enhanced immunogenicity of VIU-1005 in which lower or fewer doses were able to elicit significantly high levels of Th1-biased systemic S-specific immune responses, as demonstrated by the significant levels of binding IgG antibodies, nAbs and IFN-γ, TNF and IL-2 cytokine production from memory CD8+ and CD4+ T cells in BALB/c mice. Furthermore, compared to intradermal needle injection, which failed to induce any significant immune response, intradermal needle-free immunization elicited a robust Th1-biased humoral response similar to that observed with intramuscular immunization. Together, our results demonstrate that the synthetic VIU-1005 candidate DNA vaccine is highly immunogenic and capable of inducing long-lasting Th1-skewed humoral and cellular immunity in mice. Furthermore, we show that the use of a needle-free system could enhance the immunogenicity and minimize doses needed to induce protective immunity in mice, supporting further preclinical and clinical testing of this candidate vaccine.

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 ].…”

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

“…Multiple DNA vaccines against SARS-CoV-2 have been tested in various animal models and clinical trials (13,(39)(40)(41)(42)(43). Intramuscular vaccination with 5 mg of naked pcDNA3.1 vectored vaccines encoding different variations of the SARS-CoV-2 spike protein, including S.dTM.PP, were shown to induce neutralizing antibodies and reduce levels of viral sgmRNA in the lungs of rhesus macaques (39).…”

Improved DNA Vaccine Delivery with Needle-Free Injection Systems

“…An important advantage seen in studies using modern NFIS is that the immunogenicity elicited by jet delivery of vaccines may be enhanced compared to traditional vaccine delivery methods, partly due to the wider dispersion pattern of the injectate within tissues and more efficient delivery into cells in the case of DNA vaccines [ 35 , 47 , 50 , 51 , 52 , 53 ]. Furthermore, researchers have found dose-sparing effects from vaccines administered with NFIS, whereupon smaller doses administered with NFIS elicit similarly increased immunogenicity and protective efficacy compared to full doses delivered via either NFIS or NS [ 54 , 55 , 56 ]. Dose sparing of vaccines also represents the ability for “surge capacity” to rapidly respond to public health needs and emergencies without requiring the expansion of manufacturing capacity and scale.…”

“…SaudiVax vaccinated mice with their VIU-1005 DNA vaccine via a modified Tropis device, finding enhanced immunogenicity with an increased and long-lasting Th1-skewed humoral response and dose sparing with NFIS compared to NS ( Table 2 ) [ 55 ]. Two to three vaccinations of the lowest dose via IM Tropis elicited significant binding and neutralizing antibody responses.…”