Prospective Subunit Nanovaccine against Mycobacterium tuberculosis Infection─Cubosome Lipid Nanocarriers of Cord Factor, Trehalose 6,6' Dimycolate.

Sampa Sarkar, Abhishek Mishra, Selvakannan Periasamy, Brendan Dyett, Prashant Dogra, Andrew S Ball, Leslie Y Yeo, Jacinta F White, Zhihui Wang, Vittorio Cristini, Chinnaswamy Jagannath, Arshad Khan, Sarvesh K Soni, Calum J Drummond, Charlotte E Conn

Research output: Contribution to journalArticlepeer-review

1 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)27670-27686
Number of pages17
JournalACS Applied Materials and Interfaces
Issue number23
Early online dateJun 1 2023
StatePublished - Jun 14 2023


  • Mycobacterium tuberculosis (H37Rv)
  • cord factor trehalose 6,6′ dimycolate (TDM)
  • cubosomes
  • immune response
  • nanovaccine
  • Prospective Studies
  • Cytokines
  • Mycobacterium tuberculosis
  • Humans
  • Aged, 80 and over
  • Cord Factors/pharmacology
  • Tuberculosis/drug therapy

ASJC Scopus subject areas

  • Materials Science(all)


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