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Published on: July 25, 2022
Mesoporous Silica Nanoparticles as a Potential Platform for Vaccine Development against Tuberculosis
Sandra Montalvo-Quirós1,2, María Vallet-Regí3,4, Ainhoa Palacios5
1Department of Analytical Chemistry, Faculty of Chemistry, Complutense University of Madrid, 28040 Madrid, Spain.
Abstract:
The increasing emergence of new strains of Mycobacterium tuberculosis (Mtb) highly resistant to antibiotics constitute a public health issue, since tuberculosis still constitutes the primary cause of death in the world due to bacterial infection. Mtb has been shown to produce membrane-derived extracellular vesicles (EVs) containing proteins responsible for modulating the pathological immune response after infection. These natural vesicles were considered a promising alternative to the development of novel vaccines. However, their use was compromised by the observed lack of reproducibility between preparations. In this work, with the aim of developing nanosystems mimicking the extracellular vesicles produced by Mtb, mesoporous silica nanoparticles (MSNs) have been used as nanocarriers of immunomodulatory and vesicle-associated proteins (Ag85B, LprG and LprA). These novel nanosystems have been designed and extensively characterized, demonstrating the effectiveness of the covalent anchorage of the immunomodulatory proteins to the surface of the MSNs. The immunostimulatory capacity of the designed nanosystems has been demonstrated by measuring the levels of pro- (TNF) and anti-inflammatory (IL-10) cytokines in exposed macrophages. These results open a new possibility for the development of more complex nanosystems, including additional vesicle components or even antitubercular drugs, thus allowing for the combination of immunomodulatory and bactericidal effects against Mtb.
Insights
Researchers developed novel nanosystems using mesoporous silica nanoparticles (MSNs) to mimic Mycobacterium tuberculosis (Mtb) extracellular vesicles. These MSNs effectively deliver immunomodulatory proteins, offering a promising strategy against tuberculosis.
Area of Science:
- Nanotechnology
- Immunology
- Microbiology
Background:
- Antibiotic-resistant Mycobacterium tuberculosis (Mtb) strains pose a significant global health threat.
- Mtb produces extracellular vesicles (EVs) with immunomodulatory proteins, previously considered for vaccines but limited by preparation variability.
- Developing stable, reproducible alternatives to Mtb EVs is crucial for novel therapeutic strategies.
Purpose of the Study:
- To engineer novel nanosystems that mimic Mtb-derived EVs.
- To utilize mesoporous silica nanoparticles (MSNs) as carriers for key immunomodulatory proteins (Ag85B, LprG, LprA).
- To evaluate the immunomodulatory capacity of these protein-functionalized MSNs.
Main Methods:
- Design and characterization of MSNs functionalized with Mtb-associated proteins (Ag85B, LprG, LprA) via covalent linkage.
- Assessment of protein anchorage effectiveness on the MSN surface.
- In vitro evaluation of immunostimulatory effects using macrophage cultures, measuring pro-inflammatory (TNF) and anti-inflammatory (IL-10) cytokine levels.
Main Results:
- Successfully designed and characterized MSNs displaying covalently anchored immunomodulatory proteins.
- Demonstrated the effectiveness of protein attachment to the MSN surface.
- Confirmed the immunostimulatory capacity of the nanosystems by observing modulated cytokine production (TNF and IL-10) in macrophages.
Conclusions:
- Developed a reproducible nanosystem mimicking Mtb EVs using MSNs and immunomodulatory proteins.
- The functionalized MSNs exhibit immunostimulatory properties, indicating potential therapeutic applications.
- These findings pave the way for advanced nanosystems combining immunomodulation and bactericidal effects against Mtb.
