Targeted inhibition of Mycobacterium tuberculosis invasion into macrophages by Rv1768-Rv1983-loaded mannosylated chitosan nanoparticles.
4 affiliations
- 1Wuhan Pulmonary Hospital (Wuhan Institute for Tuberculosis Control), Hubei Branch (Wuhan Pulmonary Hospital) of the National Clinical Research Center for Infectious Diseases, Wuhan, Hubei 430030, P.R. China.
- 2State Key Laboratory of Biocatalysis and Enzyme Engineering, Department of Biochemistry and Molecular Biology, Life Science School of Hubei University, Wuhan, Hubei 430062, P.R. China.
- 3Wuhan Biocause Pharmaceutical Development Co., Ltd., Wuhan, Hubei 430056, P.R. China.
- 4Laboratory of Medical Engineering, College of Medical Technology and Engineering, Henan University of Science and Technology, Luoyang, Henan 471003, P.R. China.
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.
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BibTeX
@article{zhou2026targeted,
title = {{Targeted inhibition of Mycobacterium tuberculosis invasion into macrophages by Rv1768-Rv1983-loaded mannosylated chitosan nanoparticles.}},
author = {Jing Zhou and Mingwei An and Shidong Zhao and Yuwei Shan and Zhoubing Yu and Yun Xue and Fan Chen},
journal = {Experimental and therapeutic medicine},
year = {2026},
month = oct,
doi = {10.3892/etm.2026.13337},
url = {https://europepmc.org/article/MED/42948375},
note = {CC BY},
}
RIS
TY - JOUR
TI - Targeted inhibition of Mycobacterium tuberculosis invasion into macrophages by Rv1768-Rv1983-loaded mannosylated chitosan nanoparticles.
AU - Jing Zhou
AU - Mingwei An
AU - Shidong Zhao
AU - Yuwei Shan
AU - Zhoubing Yu
AU - Yun Xue
AU - Fan Chen
PY - 2026
DA - 2026/10/15
JO - Experimental and therapeutic medicine
DO - 10.3892/etm.2026.13337
UR - https://europepmc.org/article/MED/42948375
AB - 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.
SN - 1792-0981
SN - 1792-1015
ER -