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Front Immunol ; 12: 637654, 2021.
Article in English | MEDLINE | ID: covidwho-1138709

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.


Subject(s)
COVID-19 Vaccines/immunology , COVID-19/prevention & control , Hepatitis B Surface Antigens/genetics , Hepatitis B Surface Antigens/immunology , Mutation , Protein Domains/immunology , Protein Precursors/genetics , Protein Precursors/immunology , Recombinant Fusion Proteins/immunology , SARS-CoV-2/immunology , Vaccines, DNA/immunology , Animals , Antibodies, Neutralizing/blood , Antibodies, Neutralizing/immunology , Antibodies, Viral/blood , Antibodies, Viral/immunology , COVID-19/virology , Cell Line, Tumor , Chlorocebus aethiops , HEK293 Cells , Humans , Immunogenicity, Vaccine , Male , Mice , Mice, Inbred C57BL , Vaccination/methods , Vero Cells
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