Semi-synthetic terpenoids with differential adjuvant properties as sustainable replacements for shark squalene in vaccine emulsions
Abstract Synthetic biology has allowed for the industrial production of supply-limited sesquiterpenoids such as the antimalarial drug artemisinin and β-farnesene. One of the only unmodified animal products used in medicine is squalene, a triterpenoid derived from shark liver oil, which when formulat...
| Main Authors: | , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2023-02-01
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| Series: | npj Vaccines |
| Online Access: | https://doi.org/10.1038/s41541-023-00608-y |
| _version_ | 1827612946891538432 |
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| author | Karl J. Fisher Robert Kinsey Raodoh Mohamath Tony Phan Hong Liang Mark T. Orr William R. Lykins Jeffrey A. Guderian Julie Bakken David Argilla Gabi Ramer-Denisoff Elise Larson Yizhi Qi Sandra Sivananthan Karina Smolyar Darrick Carter Christopher J. Paddon Christopher B. Fox |
| author_facet | Karl J. Fisher Robert Kinsey Raodoh Mohamath Tony Phan Hong Liang Mark T. Orr William R. Lykins Jeffrey A. Guderian Julie Bakken David Argilla Gabi Ramer-Denisoff Elise Larson Yizhi Qi Sandra Sivananthan Karina Smolyar Darrick Carter Christopher J. Paddon Christopher B. Fox |
| author_sort | Karl J. Fisher |
| collection | DOAJ |
| description | Abstract Synthetic biology has allowed for the industrial production of supply-limited sesquiterpenoids such as the antimalarial drug artemisinin and β-farnesene. One of the only unmodified animal products used in medicine is squalene, a triterpenoid derived from shark liver oil, which when formulated into an emulsion is used as a vaccine adjuvant to enhance immune responses in licensed vaccines. However, overfishing is depleting deep-sea shark populations, leading to potential supply problems for squalene. We chemically generated over 20 squalene analogues from fermentation-derived β-farnesene and evaluated adjuvant activity of the emulsified compounds compared to shark squalene emulsion. By employing a desirability function approach that incorporated multiple immune readouts, we identified analogues with enhanced, equivalent, or decreased adjuvant activity compared to shark squalene emulsion. Availability of a library of structurally related analogues allowed elucidation of structure-function relationships. Thus, combining industrial synthetic biology with chemistry and immunology enabled generation of sustainable terpenoid-based vaccine adjuvants comparable to current shark squalene-based adjuvants while illuminating structural properties important for adjuvant activity. |
| first_indexed | 2024-03-09T08:31:29Z |
| format | Article |
| id | doaj.art-1ba5dda07550439bbc3f99d9fae12512 |
| institution | Directory Open Access Journal |
| issn | 2059-0105 |
| language | English |
| last_indexed | 2024-03-09T08:31:29Z |
| publishDate | 2023-02-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | npj Vaccines |
| spelling | doaj.art-1ba5dda07550439bbc3f99d9fae125122023-12-02T19:29:25ZengNature Portfolionpj Vaccines2059-01052023-02-018111910.1038/s41541-023-00608-ySemi-synthetic terpenoids with differential adjuvant properties as sustainable replacements for shark squalene in vaccine emulsionsKarl J. Fisher0Robert Kinsey1Raodoh Mohamath2Tony Phan3Hong Liang4Mark T. Orr5William R. Lykins6Jeffrey A. Guderian7Julie Bakken8David Argilla9Gabi Ramer-Denisoff10Elise Larson11Yizhi Qi12Sandra Sivananthan13Karina Smolyar14Darrick Carter15Christopher J. Paddon16Christopher B. Fox17Amyris, Inc.Access to Advanced Health Institute, formerly Infectious Disease Research InstituteAccess to Advanced Health Institute, formerly Infectious Disease Research InstituteInfectious Disease Research InstituteInfectious Disease Research InstituteInfectious Disease Research InstituteAccess to Advanced Health Institute, formerly Infectious Disease Research InstituteAccess to Advanced Health Institute, formerly Infectious Disease Research InstituteAccess to Advanced Health Institute, formerly Infectious Disease Research InstituteAccess to Advanced Health Institute, formerly Infectious Disease Research InstituteAccess to Advanced Health Institute, formerly Infectious Disease Research InstituteAccess to Advanced Health Institute, formerly Infectious Disease Research InstituteAccess to Advanced Health Institute, formerly Infectious Disease Research InstituteAccess to Advanced Health Institute, formerly Infectious Disease Research InstituteInfectious Disease Research InstituteInfectious Disease Research InstituteAmyris, Inc.Access to Advanced Health Institute, formerly Infectious Disease Research InstituteAbstract Synthetic biology has allowed for the industrial production of supply-limited sesquiterpenoids such as the antimalarial drug artemisinin and β-farnesene. One of the only unmodified animal products used in medicine is squalene, a triterpenoid derived from shark liver oil, which when formulated into an emulsion is used as a vaccine adjuvant to enhance immune responses in licensed vaccines. However, overfishing is depleting deep-sea shark populations, leading to potential supply problems for squalene. We chemically generated over 20 squalene analogues from fermentation-derived β-farnesene and evaluated adjuvant activity of the emulsified compounds compared to shark squalene emulsion. By employing a desirability function approach that incorporated multiple immune readouts, we identified analogues with enhanced, equivalent, or decreased adjuvant activity compared to shark squalene emulsion. Availability of a library of structurally related analogues allowed elucidation of structure-function relationships. Thus, combining industrial synthetic biology with chemistry and immunology enabled generation of sustainable terpenoid-based vaccine adjuvants comparable to current shark squalene-based adjuvants while illuminating structural properties important for adjuvant activity.https://doi.org/10.1038/s41541-023-00608-y |
| spellingShingle | Karl J. Fisher Robert Kinsey Raodoh Mohamath Tony Phan Hong Liang Mark T. Orr William R. Lykins Jeffrey A. Guderian Julie Bakken David Argilla Gabi Ramer-Denisoff Elise Larson Yizhi Qi Sandra Sivananthan Karina Smolyar Darrick Carter Christopher J. Paddon Christopher B. Fox Semi-synthetic terpenoids with differential adjuvant properties as sustainable replacements for shark squalene in vaccine emulsions npj Vaccines |
| title | Semi-synthetic terpenoids with differential adjuvant properties as sustainable replacements for shark squalene in vaccine emulsions |
| title_full | Semi-synthetic terpenoids with differential adjuvant properties as sustainable replacements for shark squalene in vaccine emulsions |
| title_fullStr | Semi-synthetic terpenoids with differential adjuvant properties as sustainable replacements for shark squalene in vaccine emulsions |
| title_full_unstemmed | Semi-synthetic terpenoids with differential adjuvant properties as sustainable replacements for shark squalene in vaccine emulsions |
| title_short | Semi-synthetic terpenoids with differential adjuvant properties as sustainable replacements for shark squalene in vaccine emulsions |
| title_sort | semi synthetic terpenoids with differential adjuvant properties as sustainable replacements for shark squalene in vaccine emulsions |
| url | https://doi.org/10.1038/s41541-023-00608-y |
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