Abstract
A novel STING agonist, CDGSF, ipsilaterally modified with phosphorothioate and fluorine, was synthesized. The phosphorothioate in CDGSF might be a site for covalent conjugation. Injection of CDGSF generated an immunogenic ("hot") tumor microenvironment to suppress melanoma, more efficiently than dithio CDG. In particular, immunization with SARS-CoV-2 spike protein using CDGSF as an adjuvant elicited an exceptionally high antibody titer and a robust T cell response, overcoming the drawbacks of aluminum hydroxide. These results highlighted the therapeutic potential of CDGSF for cancer immunotherapy and the adjuvant potential of the STING agonist in the SARS-CoV-2 vaccine for the first time.
MeSH terms
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Adjuvants, Immunologic / administration & dosage*
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Adjuvants, Immunologic / chemical synthesis
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Aluminum Hydroxide / administration & dosage
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Aluminum Hydroxide / chemistry
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Animals
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Antibodies, Viral / biosynthesis
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B-Lymphocytes / drug effects
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B-Lymphocytes / immunology
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B-Lymphocytes / virology
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COVID-19 / immunology
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COVID-19 / prevention & control*
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COVID-19 / virology
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COVID-19 Vaccines / administration & dosage*
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COVID-19 Vaccines / chemistry
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Enzyme-Linked Immunospot Assay
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Humans
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Immunotherapy / methods
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Interferon-gamma / biosynthesis
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Melanoma, Experimental / drug therapy*
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Melanoma, Experimental / immunology
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Melanoma, Experimental / mortality
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Melanoma, Experimental / pathology
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Membrane Proteins / agonists*
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Membrane Proteins / genetics
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Membrane Proteins / immunology
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Mice
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Nucleotides, Cyclic / administration & dosage*
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Nucleotides, Cyclic / chemical synthesis
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SARS-CoV-2 / drug effects
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SARS-CoV-2 / immunology
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SARS-CoV-2 / pathogenicity
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Skin Neoplasms / drug therapy*
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Skin Neoplasms / immunology
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Skin Neoplasms / mortality
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Skin Neoplasms / pathology
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Spike Glycoprotein, Coronavirus / administration & dosage
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Spike Glycoprotein, Coronavirus / chemistry
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Spike Glycoprotein, Coronavirus / immunology
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Survival Analysis
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T-Lymphocytes / drug effects
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T-Lymphocytes / immunology
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T-Lymphocytes / virology
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Tumor Burden / drug effects
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Tumor Microenvironment / drug effects
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Tumor Microenvironment / immunology
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Vaccination / methods
Substances
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Adjuvants, Immunologic
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Antibodies, Viral
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COVID-19 Vaccines
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Membrane Proteins
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Nucleotides, Cyclic
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STING1 protein, human
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Spike Glycoprotein, Coronavirus
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spike protein, SARS-CoV-2
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Aluminum Hydroxide
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Interferon-gamma