Abstract
A coronavirus SARS-CoV-2, which has caused the pandemic viral pneumonia disease COVID-19, significantly threatens global public health, highlighting the need to develop effective and safe vaccines against its infection. In this study, we developed a novel DNA vaccine candidate against SARS-CoV-2 by expressing a chimeric protein of its receptor-binding domain (RBD) fused to a 33-bp sequence (11 aa) from the hepatitis B virus (HBV) preS1 region with a W4P mutation (W4P-RBD) at the N-terminal region and evaluated its immunogenicity. In vitro transfection experiments in multiple cell lines demonstrated that W4P-RBD vs. wild-type RBD protein (W-RBD) led to enhanced production of IL-6 and TNFα at the transcription and translation levels, suggesting the adjuvant potential of N-terminal HBV preS1 sequences for DNA vaccines against SARS-CoV-2. W4P-RBD also led to enhanced production of IgG and IgA, which can neutralize and block SARS-CoV-2 infection in both blood sera and bronchoalveolar lavage (BAL) fluid from the lung in vaccinated mice. Additionally, W4P-RBD led to an enhanced T-cell-mediated cellular immune response under S1 protein stimulation. In summary, W4P-RBD led to robust humoral and cell-mediated immune responses against SARS-CoV-2 in vaccinated mice, highlighting its feasibility as a novel DNA vaccine to protect against SARS-CoV-2 infection.
Highlights
The coronavirus disease 2019 or COVID-19 pandemic is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) [1,2,3,4,5], highlighting the need to develop effective and safe vaccines against its infection
Design and Construction of the hepatitis B virus (HBV) W4P preS1-Fused pcDNA3.3-receptor-binding domain (RBD) Plasmid (W4P-RBD) as a DNA Vaccine Candidate for SARS-CoV-2
We measured the expression of the encoded SARS-CoV-2 RBD transgene at the protein level in Vero E6, Huh7, and 293T cells transfected with the constructed plasmids wild-type RBD protein (W-RBD) and W4P-RBD via Western blot analysis using an antibody against SARS-CoV-2 RBD in cell lysates
Summary
The coronavirus disease 2019 or COVID-19 pandemic is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) [1,2,3,4,5], highlighting the need to develop effective and safe vaccines against its infection. The SARS-CoV-2 spike (S) protein consists of S1, including the receptor-binding domain (RBD) and S2 subunits [8]. The RBD in both SARS-CoV and SARS-CoV-2 infections is required for ACE2 receptor docking [6, 9,10,11], and most of the potent neutralizing monoclonal antibodies have been produced against the. Several RBD-targeting vaccines against SARS-CoV-2 include mRNA- [15, 16] or protein-based subunit vaccines [17, 18]. To develop RBD-based DNA vaccines, strategies to promote immunogenicity, including the use of appropriate adjuvants or addition of exogenous sequences capable of potentiating immune responses, should be combined [20,21,22,23,24,25]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
