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Evaluation of the Immunoadjuvant Effects of miR-155-Chitosan Polyplex on Leishmania major Infected Mice
Azam Pourabbasi Ardekan1, Ali Haghighi1, Samira Mohammadi-Yeganeh2,3
1Department of Parasitology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Background:
MicroRNAs have gained attention as key immunomodulators, with miR-155 specifically shown in various studies to drive macrophage polarization toward the classical phenotype. This polarization is crucial, as classical macrophages play a well-recognized role in differentiating type-1 immune responses and resisting Leishmania infection.
Objective:
The present study aims to evaluate the anti-leishmanial immunoadjuvant effects of the miR-155 chitosan polyplex (miR-155 CP).
Methods:
The anti-leishmanial immunoadjuvant activity of miR-155 CP synthesized by the coacervation method was assessed against L. major (MRHO/IR/75/ER) by analyzing the infectivity rate on RAW 264.7 cells in vitro.MiR-155 CP as an adjuvant co-administrated with soluble Leishmania antigen (SLA) for immunization of BALB/c mice, then the challenge was performed by subcutaneous injection of 1 × 106 L. major promastigotes. Eight weeks following the challenge, lesion size, parasite load, cytokine assay, and nitric oxide production were evaluated.
Results:
The nanoparticles were produced with a size of 233.87 ± 8 nm and a zeta potential of + 22.6 ± 2 mV with good transfection efficiency. The mean infection index among pretreated cells with miR-155 CP (72±1.1) decreased significantly compared to the control group (420 ± 2.8). The parasite burden and the size of the lesions were significantly reduced in the immunized infected mice. Vaccination by miR-155 CP/SLA triggered the production of IFN-γ and NO and changed the cytokine profile of antigen-specific cells.Conclusion:The effectiveness of the SLA vaccine can be enhanced by including miR-155 CP as an adjuvant. SLA and miR-155 CP co-administration improve the type-1 immune response. This enhanced immune response helps prevent severe leishmaniasis.
Insights
The miR-155 chitosan polyplex (miR-155 CP) enhances the Leishmania vaccine by boosting type-1 immunity. This adjuvant therapy reduces parasite load and lesion size, offering a promising strategy against leishmaniasis.
Area of Science:
- Immunology
- Parasitology
- Nanotechnology
Background:
- MicroRNAs, particularly miR-155, are key immunomodulators that promote classical macrophage polarization.
- Classical macrophages are vital for type-1 immune responses and resistance to Leishmania infection.
Purpose of the Study:
- To evaluate the anti-leishmanial immunoadjuvant effects of miR-155 chitosan polyplex (miR-155 CP).
Main Methods:
- Synthesized miR-155 CP using coacervation and assessed its anti-leishmanial activity against L. major in vitro.
- Administered miR-155 CP with soluble Leishmania antigen (SLA) to BALB/c mice for immunization, followed by L. major challenge.
- Evaluated lesion size, parasite load, cytokine production (IFN-γ), and nitric oxide (NO) levels post-challenge.
Main Results:
- miR-155 CP nanoparticles exhibited good transfection efficiency, significantly reducing the infection index in vitro.
- Immunization with miR-155 CP/SLA significantly decreased parasite burden and lesion size in mice.
- Vaccination induced a type-1 immune response, characterized by increased IFN-γ and NO production.
Conclusions:
- miR-155 CP serves as an effective immunoadjuvant, enhancing the efficacy of the SLA vaccine.
- Co-administration of SLA and miR-155 CP boosts type-1 immunity, crucial for preventing severe leishmaniasis.
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