Mesoporous Silica Nanoparticles as a Potential Platform for Vaccine Development against Tuberculosis.
Author: Montalvo Quiros, Sandra; Vallet Regí, María; Palacios, Ainhoa; Anguita, Juan; Prados Rosales, Rafael; González, Blanca; Luque García, José L.
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 e ectiveness 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 e ects against Mtb.
Universal identifier: http://hdl.handle.net/10641/2369
Date: 2020
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