Targeted inhibition of Mycobacterium tuberculosis invasion into macrophages by Rv1768‑Rv1983‑loaded mannosylated chitosan nanoparticles
Year: 2026
Type: article
Abstract: Tuberculosis (TB) remains a major threat to global health.The protective efficacy of the Bacillus Calmette-Guérin vaccine is limited because of the absence of multiple virulence-related genomic regions in Mycobacterium tuberculosis (MTB).The surface proteins of MTB are closely associated with bacterial invasiveness and pathogenicity, representing promising targets for novel vaccine development.In the present study, the MTB polymorphic GC-rich sequence proteins (Pro-Glu and Pro-Pro-Glu-Pro-Arg-Gly-Ser) family fusion protein Rv1768-Rv1983 was cloned, expressed and encapsulated into mannosylated chitosan (MCS) to construct MCS-Rv1768Rv1983 nanoparticles.The immunological and protective effects of this nanoformulation were evaluated in vitro and in a mouse model.Physicochemical characterization revealed that the nanoparticles had a mean particle size of 196.3 nm and a drug loading efficiency of 8.02%.In vitro cell experiments demonstrated that MCS-Rv1768-Rv1983 exhibited no obvious cytotoxicity and stimulated CD4 + T cells to secrete IFN-γ and IL-4, as well as CD8 + T cells, to produce IFN-γ.Animal experiments revealed that immunization with MCS-Rv1768-Rv1983 markedly elevated serum IgG1 and IgG2a titres and that the induced antibodies significantly reduced the invasion of virulent MTB H37Rv into macrophages.After H37Rv challenge, compared with the control group, the MCS-Rv1768-Rv1983 immunization group exhibited significantly lower bacterial loads in mouse lungs and markedly longer survival times.These results confirm that MCS nanoparticles can increase the immune efficacy of the Rv1768-Rv1983 fusion protein, block MTB invasion into macrophages and may contribute to the early clearance of MTB by macrophages.
Language: English
Subfield: Infectious Diseases
Field: Medicine
Domain: Health Sciences
Open Access status: diamond
OpenAlex ID: W7222080510