Prospective Subunit Nanovaccine against Mycobacterium tuberculosis Infection─Cubosome Lipid Nanocarriers of Cord Factor, Trehalose 6,6′ Dimycolate,ACS Applied Materials & Interfaces

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Prospective Subunit Nanovaccine against Mycobacterium tuberculosis Infection─Cubosome Lipid Nanocarriers of Cord Factor, Trehalose 6,6′ Dimycolate
ACS Applied Materials & Interfaces ( IF 8.3 ) Pub Date : 2023-06-01 , DOI: 10.1021/acsami.3c04063
Sampa Sarkar ₁ , Abhishek Mishra ₂ , Selvakannan Periasamy ₁ , Brendan Dyett ₁ , Prashant Dogra _{3,

4} , Andrew S Ball ₁ , Leslie Y Yeo ₅ , Jacinta F White ₆ , Zhihui Wang _{3,

4,

7} , Vittorio Cristini _{3,

7,

8,

9} , Chinnaswamy Jagannath ₂ , Arshad Khan ₂ , Sarvesh K Soni ₁ , Calum J Drummond ₁ , Charlotte E Conn ₁

Affiliation

An improved vaccine is urgently needed to replace the now more than 100-year-old Bacillus Calmette–Guérin (BCG) vaccine against tuberculosis (TB) disease, which represents a significant burden on global public health. Mycolic acid, or cord factor trehalose 6,6′ dimycolate (TDM), a lipid component abundant in the cell wall of the pathogen Mycobacterium tuberculosis (MTB), has been shown to have strong immunostimulatory activity but remains underexplored due to its high toxicity and poor solubility. Herein, we employed a novel strategy to encapsulate TDM within a cubosome lipid nanocarrier as a potential subunit nanovaccine candidate against TB. This strategy not only increased the solubility and reduced the toxicity of TDM but also elicited a protective immune response to control MTB growth in macrophages. Both pre-treatment and concurrent treatment of the TDM encapsulated in lipid monoolein (MO) cubosomes (MO–TDM) (1 mol %) induced a strong proinflammatory cytokine response in MTB-infected macrophages, due to epigenetic changes at the promoters of tumor necrosis factor alpha (TNF-α) and interleukin 6 (IL-6) in comparison to the untreated control. Furthermore, treatment with MO–TDM (1 mol %) cubosomes significantly improved antigen processing and presentation capabilities of MTB-infected macrophages to CD4 T cells. The ability of MO–TDM (1 mol %) cubosomes to induce a robust innate and adaptive response in vitro was further supported by a mathematical modeling study predicting the vaccine efficacy in vivo. Overall, these results indicate a strong immunostimulatory effect of TDM when delivered through the lipid nanocarrier, suggesting its potential as a novel TB vaccine.

中文翻译：

抗结核分枝杆菌感染的前瞻性亚基纳米疫苗─脐带因子、海藻糖 6,6' 二菌酸酯的立方体脂质纳米载体

迫切需要一种改进的疫苗来取代已有 100 多年历史的卡介苗 (BCG) 疫苗，以对抗结核病 (TB)，这对全球公共卫生构成了沉重负担。分枝菌酸，或索因子海藻糖 6,6' 二分枝菌酸酯 (TDM)，一种在病原体结核分枝杆菌的细胞壁中丰富的脂质成分(MTB)，已被证明具有很强的免疫刺激活性，但由于其高毒性和溶解性差，仍未得到充分探索。在此，我们采用了一种新策略将 TDM 封装在立方体脂质纳米载体中，作为潜在的抗结核亚基纳米疫苗候选物。该策略不仅增加了 TDM 的溶解度并降低了毒性，而且还引发了保护性免疫反应以控制 MTB 在巨噬细胞中的生长。由于肿瘤坏死启动子的表观遗传变化，封装在脂质单油酸甘油酯 (MO) 立方体 (MO–TDM) (1 mol %) 中的 TDM 的预处理和同时处理在 MTB 感染的巨噬细胞中诱导了强烈的促炎细胞因子反应与未处理的对照相比，α 因子 (TNF-α) 和白细胞介素 6 (IL-6)。此外，用 MO–TDM (1 mol %) 立方体处理可显着改善抗原加工和 MTB 感染的巨噬细胞向 CD4 T 细胞的呈递能力。MO-TDM (1 mol %) 立方体在体外诱导强大的先天性和适应性反应的能力得到了预测体内疫苗效力的数学模型研究的进一步支持。总的来说，这些结果表明，当通过脂质纳米载体递送时，TDM 具有很强的免疫刺激作用，表明其作为新型 TB 疫苗的潜力。

更新日期：2023-06-01

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