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.
Highlights
Since its emergence in December 2019, the coronavirus disease 2019 (COVID-19) pandemic has caused ∼170 million infections with nearly more than 3.5 million deaths worldwide as of June 2021
We developed a synthetic codon-optimized DNA vaccine, denoted “VIU-1005,” as a countermeasure to aid in controlling SARSCoV-2 spread
To further improve the immunogenicity of the naked synthetic DNA vaccine and minimize the number and size of doses, we investigated the use of a needle-free Tropis system with our vaccine in BALB/c mice in a separate experiment (Figure 5A)
Summary
Since its emergence in December 2019, the coronavirus disease 2019 (COVID-19) pandemic has caused ∼170 million infections with nearly more than 3.5 million deaths worldwide as of June 2021. A novel betacoronavirus (beta-CoV) known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was identified as the causative agent of COVID-19 (Lu et al, 2020; Zhu et al, 2020). SARS-CoV-2 can cause a wide spectrum of disease manifestations in individuals from different age groups. Some patients can suffer from moderate to severe life-threatening acute respiratory distress syndrome (ARDS) with possible fatal outcomes (Jin et al, 2020; Rodriguez-Morales et al, 2020; Wang et al, 2020). The high human-to-human transmission rate of SARS-CoV-2 poses a major challenge toward controlling its spread (Adhikari et al, 2020; Bai et al, 2020; Xu et al, 2020b)
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