Assessment of immunogenicity and protective efficiency of multi-epitope antigen-loaded in mannan decorated PLGA nanoparticles against tuberculosis.

Abstract

The antigen-targeting to dendritic cells (DCs) has gained increasing attention as the potential approach for immunotherapy in recent years due to the ability of DCs to regulate innate and adaptive immunity. In the present study, the immunogenicity and protective efficiency of mannan-decorated PLGA nanoparticles (NPs) loaded with multi-epitopes mycobacterium tuberculosis antigen (HspX-Ppe44-EsxV) were evaluated as a targeted delivery system to DCs. For this purpose, PLGA nanoparticle formulations were prepared and subsequently decorated by mannan. The physicochemical properties and level of mannan incorporation, as well as encapsulation efficiency and antigen release, were assessed. The potential of formulated NPs for antigen targeting to DCs, and immunogenicity against tuberculosis (TB) were investigated using immunofluorescence assay and in-vivo experiments. Mannan incorporation enhanced the uptake of fusion-loaded PLGA by DCs. The cytokine and antibody assays demonstrated that mannosylation of NPs and BCG-primed mice boosted by mannan-PLGA could significantly elevate Th1-biased immune responses relative to the BCG and non-modified PLGA NPs. Our findings also proved that the mannosylated vaccine in the presence of CpG could evoke Th1 and Th17 responses with appropriate protective efficiency against TB in mice. This result illustrated that the active targeting of DCs by mannan-PLGA NPs could induce a proper anti-tuberculosis response, which is essential for protection against tuberculosis.