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.
【저자키워드】 COVID-19, SARS-CoV-2, Receptor-binding domain (RBD), DNA vaccine, HBV preS1, W4P-RBD, 【초록키워드】 IgG, Vaccine, coronavirus, pandemic, Mutation, Pneumonia, translation, feasibility, Cellular immune response, IL-6, SARS-COV-2 infection, Transcription, Infection, lung, coronavirus SARS-CoV-2, HBV, Viral pneumonia, BAL, Protein, Viral, Receptor-binding domain, mice, RBD, IgA, immune responses, sera, hepatitis B, experiment, disease, Blood, RBD protein, Hepatitis B virus, Bronchoalveolar lavage, Safe, humoral, chimeric, global public health, domain, sequence, TNFα, wild-type, S1 protein, cell-mediated immune response, N-terminal, effective, neutralize, robust, PROTECT, develop, caused, significantly, evaluated, demonstrated, expressing, highlighting, fused, multiple cell line, 【제목키워드】 DNA, Region, RBD, novel, encoding, Against,