Semi-synthetic terpenoids with differential adjuvant properties as sustainable replacements for shark squalene in vaccine emulsions.
Semi-synthetic terpenoids with differential adjuvant properties as sustainable replacements for shark squalene in vaccine emulsions.
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DOI：
10.1038/s41541-023-00608-y
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发表时间：
2023-02-16
期刊：
影响因子：
9.2
通讯作者：
中科院分区：
文献类型：
--
作者：
合成生物学使供应有限的倍半萜类化合物，如抗疟疾药物青蒿素和β-法呢烯的工业生产成为可能。在医学中使用的唯一未经修饰的动物产品之一是角鲨烯，这是一种从鲨鱼肝油中提取的三萜类化合物，当配制成乳剂时，可用作疫苗佐剂，以增强许可疫苗的免疫反应。然而，过度捕捞正在耗尽深海鲨鱼种群，导致潜在的角鲨烯供应问题。我们从发酵衍生的β-法呢烯化学地产生了超过20种角鲨烯类似物，并且与鲨鱼角鲨烯乳剂相比评估了乳化化合物的佐剂活性。通过采用纳入多个免疫读数的期望函数方法，我们鉴定了与鲨鱼角鲨烯乳剂相比具有增强的、等同的或降低的佐剂活性的类似物。结构相关的类似物库的可用性允许阐明结构-功能关系。因此，将工业合成生物学与化学和免疫学相结合，能够产生可持续的基于萜类化合物的疫苗佐剂，与目前的基于鲨鱼角鲨烯的佐剂相当，同时阐明对佐剂活性重要的结构特性。
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.
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影响因子：
64.8
作者：
Pacoureau, Nathan;Rigby, Cassandra L.;Dulvy, Nicholas K.
通讯作者：
Dulvy, Nicholas K.
辅助大流行性流感疫苗：乳液成分的变化会影响稳定性，抗原结构和疫苗功效。
影响因子：
4.4
作者：
Fox CB;Barnes V L;Evers T;Chesko JD;Vedvick TS;Coler RN;Reed SG;Baldwin SL
通讯作者：
Baldwin SL
DOI：
10.1016/b978-0-12-416003-3.00014-7
发表时间：
2012-01-01
期刊：
ADVANCES IN FOOD AND NUTRITION RESEARCH, VOL 65: MARINE MEDICINAL FOODS: IMPLICATIONS AND APPLICATIONS - ANIMALS AND MICROBES
影响因子：
--
作者：
Kim, Se-Kwon;Karadeniz, Fatih
通讯作者：
Karadeniz, Fatih
影响因子：
13.8
作者：
NAYLER, JHC
通讯作者：
NAYLER, JHC
影响因子：
7.7
作者：
Kim, Eui Ho;Woodruff, Matthew C.;Pulendran, Bali
通讯作者：
Pulendran, Bali