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Rv2299c, a novel dendritic cell-activating antigen of Mycobacterium tuberculosis, fused-ESAT-6 subunit vaccine confers improved and durable protection against the hypervirulent strain HN878 in mice

Authors
 Han-Gyu Choi  ;  Seunga Choi  ;  Yong Woo Back  ;  Seungwha Paik  ;  Hye-Soo Park  ;  Woo Sik Kim,2 Hongmin Kim,2 Seung Bin Cha,2 Chul Hee Choi,1 Sung Jae Shin,2 and Hwa-Jung Kim1 
Citation
 ONCOTARGET , Vol.8(12) : 19947-19967, 2017 
Journal Title
ONCOTARGET
Issue Date
2017
MeSH
Animals ; Antigens, Bacterial/immunology* ; BCG Vaccine/administration & dosage ; BCG Vaccine/immunology* ; Bacterial Proteins/immunology* ; CD4-Positive T-Lymphocytes/immunology ; Cell Differentiation ; Cells, Cultured ; Cytokines/metabolism ; Dendritic Cells/immunology* ; Female ; Immunologic Memory/immunology ; Mice ; Mice, Inbred C57BL ; Mycobacterium tuberculosis/immunology* ; Mycobacterium tuberculosis/pathogenicity ; Recombinant Fusion Proteins/immunology ; Th1 Cells/immunology ; Tuberculosis, Pulmonary/immunology ; Tuberculosis, Pulmonary/microbiology ; Tuberculosis, Pulmonary/prevention & control* ; Vaccines, Subunit/therapeutic use*
Keywords
DC maturation ; Toll-like receptor 4 ; multifunctional T cell ; subunit vaccine ; tuberculosis
Abstract
Understanding functional interactions between DCs and antigens is necessary for achieving an optimal and desired immune response during vaccine development. Here, we identified and characterized protein Rv2299c (heat-shock protein 90 family), which effectively induced DC maturation. The Rv2299c-maturated DCs showed increased expression of surface molecules and production of proinflammatory cytokines. Rv2299c induced these effects by binding to TLR4 and stimulating the downstream MyD88-, MAPK- and NF-κB-dependent signaling pathways. The Rv2299c-maturated DCs also showed an induced Th1 cell response with bactericidal activity and expansion of effector/memory T cells. The Rv2299c-ESAT-6 fused protein had greater immunoreactivity than ESAT-6. Furthermore, boosting BCG with the fused protein significantly reduced hypervirulent Mycobacterium tuberculosis HN878 burdens post-challenge. The pathological study of the lung from the challenged mice assured the efficacy of the fused protein. The fused protein boosting also induced Rv2299c-ESAT-6-specific multifunctional CD4+ T-cell response in the lungs of the challenged mice. Our findings suggest that Rv2299c is an excellent candidate for the rational design of an effective multiantigenic TB vaccine.
Files in This Item:
T201702169.pdf Download
DOI
10.18632/oncotarget.15256
Appears in Collections:
1. College of Medicine (의과대학) > Research Institute (부설연구소) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Microbiology (미생물학교실) > 1. Journal Papers
Yonsei Authors
Shin, Sung Jae(신성재) ORCID logo https://orcid.org/0000-0003-0854-4582
Cha, Seung Bin(차승빈)
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/154286
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