Abstract
The coronavirus 2019 (COVID-19) pandemic is causing serious impacts in the world, and safe and effective vaccines and medicines are the best methods to combat the disease. The receptor-binding domain (RBD) of the SARS-CoV-2 spike protein plays a key role in interacting with the angiotensin-converting enzyme 2 (ACE2) receptor, and is regarded as an important target of vaccines. Herein, we constructed the adjuvant-protein conjugate Pam3CSK4-RBD as a vaccine candidate, in which the N-terminal of the RBD was site-selectively oxidized by transamination and conjugated with the TLR1/2 agonist Pam3CSK4. This demonstrated that the conjugation of Pam3CSK4 significantly enhanced the anti-RBD antibody response and cellular response. In addition, sera from the Pam3CSK4-RBD immunized group efficiently inhibited the binding of the RBD to ACE2 and protected cells from SARS-CoV-2 and four variants of concern (alpha, beta, gamma and delta), indicating that this adjuvant strategy could be one of the effective means for protein vaccine development.
MeSH terms
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Angiotensin-Converting Enzyme 2 / metabolism
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Animals
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Antibody Formation
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Antigens, CD / metabolism
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Antigens, Differentiation, Myelomonocytic / metabolism
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COVID-19 / prevention & control*
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COVID-19 / virology
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Female
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HEK293 Cells
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Humans
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Lipopeptides / chemistry*
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Macrophages / cytology
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Macrophages / immunology
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Macrophages / metabolism
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Mice
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Mice, Inbred BALB C
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Protein Binding
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Protein Domains / immunology
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RAW 264.7 Cells
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Recombinant Proteins / biosynthesis
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Recombinant Proteins / immunology
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SARS-CoV-2 / immunology*
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SARS-CoV-2 / isolation & purification
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SARS-CoV-2 / metabolism
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Spike Glycoprotein, Coronavirus / chemistry*
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Spike Glycoprotein, Coronavirus / genetics
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Spike Glycoprotein, Coronavirus / immunology
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Spike Glycoprotein, Coronavirus / metabolism
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Vaccines, Conjugate / administration & dosage
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Vaccines, Conjugate / chemistry
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Vaccines, Conjugate / immunology*
Substances
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Antigens, CD
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Antigens, Differentiation, Myelomonocytic
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CD68 protein, mouse
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Lipopeptides
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Pam(3)CSK(4) peptide
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Recombinant Proteins
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Spike Glycoprotein, Coronavirus
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Vaccines, Conjugate
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spike protein, SARS-CoV-2
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ACE2 protein, human
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Angiotensin-Converting Enzyme 2