Emulsion adjuvant-induced uric acid release modulates optimal immunogenicity by targeting dendritic cells and B cells
Abstract Squalene-based emulsion (SE) adjuvants like MF59 and AS03 are used in protein subunit vaccines against influenza virus (e.g., Fluad, Pandemrix, Arepanrix) and SARS-CoV-2 (e.g., Covifenz, SKYCovione). We demonstrate the critical role of uric acid (UA), a damage-associated molecular pattern (...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-04-01
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| Series: | npj Vaccines |
| Online Access: | https://doi.org/10.1038/s41541-025-01130-z |
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| author | Sun Min Lee Junghwa Lee Dong-In Kim Jonathan P. Avila Helder Nakaya Kihyuck Kwak Eui Ho Kim |
| author_facet | Sun Min Lee Junghwa Lee Dong-In Kim Jonathan P. Avila Helder Nakaya Kihyuck Kwak Eui Ho Kim |
| author_sort | Sun Min Lee |
| collection | DOAJ |
| description | Abstract Squalene-based emulsion (SE) adjuvants like MF59 and AS03 are used in protein subunit vaccines against influenza virus (e.g., Fluad, Pandemrix, Arepanrix) and SARS-CoV-2 (e.g., Covifenz, SKYCovione). We demonstrate the critical role of uric acid (UA), a damage-associated molecular pattern (DAMP), in triggering immunogenicity by SE adjuvants. In mice, SE adjuvants elevated DAMP levels in draining lymph nodes. Strikingly, inhibition of UA synthesis reduced vaccine-induced innate immunity, subsequently impairing optimal antibody and T cell responses. In vivo treatment with UA crystals elicited partial adjuvant effects. In vitro stimulation with UA crystals augmented the activation of dendritic cells (DCs) and B cells and altered multiple pathways in these cells, including inflammation and antigen presentation in DCs and cell proliferation in B cells. In an influenza vaccine model, UA contributed to protection against influenza viral infection. These results demonstrate the importance of DAMPs, specifically the versatile role of UA in the immunogenicity of SE adjuvants, by regulating DCs and B cells. |
| format | Article |
| id | doaj-art-be1b44632630489d9f6bf968cf694d43 |
| institution | OA Journals |
| issn | 2059-0105 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | npj Vaccines |
| spelling | doaj-art-be1b44632630489d9f6bf968cf694d432025-08-20T02:24:26ZengNature Portfolionpj Vaccines2059-01052025-04-0110111510.1038/s41541-025-01130-zEmulsion adjuvant-induced uric acid release modulates optimal immunogenicity by targeting dendritic cells and B cellsSun Min Lee0Junghwa Lee1Dong-In Kim2Jonathan P. Avila3Helder Nakaya4Kihyuck Kwak5Eui Ho Kim6Viral Immunology Laboratory, Institut Pasteur KoreaViral Immunology Laboratory, Institut Pasteur KoreaViral Immunology Laboratory, Institut Pasteur KoreaDepartment of Clinical and Toxicological Analysis, School of Pharmaceutical Sciences, University of São PauloDepartment of Clinical and Toxicological Analysis, School of Pharmaceutical Sciences, University of São PauloDepartment of Microbiology and Immunology, Yonsei University College of MedicineViral Immunology Laboratory, Institut Pasteur KoreaAbstract Squalene-based emulsion (SE) adjuvants like MF59 and AS03 are used in protein subunit vaccines against influenza virus (e.g., Fluad, Pandemrix, Arepanrix) and SARS-CoV-2 (e.g., Covifenz, SKYCovione). We demonstrate the critical role of uric acid (UA), a damage-associated molecular pattern (DAMP), in triggering immunogenicity by SE adjuvants. In mice, SE adjuvants elevated DAMP levels in draining lymph nodes. Strikingly, inhibition of UA synthesis reduced vaccine-induced innate immunity, subsequently impairing optimal antibody and T cell responses. In vivo treatment with UA crystals elicited partial adjuvant effects. In vitro stimulation with UA crystals augmented the activation of dendritic cells (DCs) and B cells and altered multiple pathways in these cells, including inflammation and antigen presentation in DCs and cell proliferation in B cells. In an influenza vaccine model, UA contributed to protection against influenza viral infection. These results demonstrate the importance of DAMPs, specifically the versatile role of UA in the immunogenicity of SE adjuvants, by regulating DCs and B cells.https://doi.org/10.1038/s41541-025-01130-z |
| spellingShingle | Sun Min Lee Junghwa Lee Dong-In Kim Jonathan P. Avila Helder Nakaya Kihyuck Kwak Eui Ho Kim Emulsion adjuvant-induced uric acid release modulates optimal immunogenicity by targeting dendritic cells and B cells npj Vaccines |
| title | Emulsion adjuvant-induced uric acid release modulates optimal immunogenicity by targeting dendritic cells and B cells |
| title_full | Emulsion adjuvant-induced uric acid release modulates optimal immunogenicity by targeting dendritic cells and B cells |
| title_fullStr | Emulsion adjuvant-induced uric acid release modulates optimal immunogenicity by targeting dendritic cells and B cells |
| title_full_unstemmed | Emulsion adjuvant-induced uric acid release modulates optimal immunogenicity by targeting dendritic cells and B cells |
| title_short | Emulsion adjuvant-induced uric acid release modulates optimal immunogenicity by targeting dendritic cells and B cells |
| title_sort | emulsion adjuvant induced uric acid release modulates optimal immunogenicity by targeting dendritic cells and b cells |
| url | https://doi.org/10.1038/s41541-025-01130-z |
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