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

Sawsan S Alamri; Khalid A Alluhaybi; Rowa Y Alhabbab; Mohammad Basabrain; Abdullah Algaissi; Sarah Almahboub; Mohamed A Alfaleh; Turki S Abujamel; Wesam H Abdulaal; M-Zaki ElAssouli; Rahaf H Alharbi; Mazen Hassanain; Anwar M Hashem

doi:10.3389/fmicb.2021.727455

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

Front Microbiol. 2021 Sep 7:12:727455. doi: 10.3389/fmicb.2021.727455. eCollection 2021.

Authors

Sawsan S Alamri^{1

2}, Khalid A Alluhaybi^{1

3}, Rowa Y Alhabbab^{1

4}, Mohammad Basabrain¹, Abdullah Algaissi^{5

6}, Sarah Almahboub^{1

7}, Mohamed A Alfaleh^{1

3}, Turki S Abujamel^{1

4}, Wesam H Abdulaal², M-Zaki ElAssouli¹, Rahaf H Alharbi¹, Mazen Hassanain^{7

8}, Anwar M Hashem^{1

9}

Affiliations

¹ Vaccines and Immunotherapy Unit, King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia.
² Department of Biochemistry, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia.
³ Faculty of Pharmacy, King Abdulaziz University, Jeddah, Saudi Arabia.
⁴ Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah, Saudi Arabia.
⁵ Department of Medical Laboratories Technology, College of Applied Medical Sciences, Jazan University, Jazan, Saudi Arabia.
⁶ Medical Research Center, Jazan University, Jazan, Saudi Arabia.
⁷ SaudiVax Ltd., Thuwal, Saudi Arabia.
⁸ Department of Surgery, Faculty of Medicine, King Saud University, Riyadh, Saudi Arabia.
⁹ Department of Medical Microbiology and Parasitology, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia.

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.

Keywords: COVID-19; SARS-CoV-2; plasmid DNA; preclinical (in vivo) studies; spike (S) glycoprotein.