Enhanced protection against tuberculosis by vaccination with recombinant BCG over-expressing HspX protein.
Immunization with Mycobacterium bovis Bacille Calmette-Guerin (BCG) did not induce adequate Th1 responses to the latency antigen, HspX of M. tuberculosis. To increase the immunogenicity and protective efficacy of BCG, a recombinant BCG strain over-expressing antigen HspX (rBCG::X) was constructed. The recombinant strain rBCG::X expressed high levels of both HspX protein in the cytosol and Ag85B protein in the cytosol and supernatant. Mice vaccinated with rBCG::X produced a more consistent and enduring protective effect against infection with M. tuberculosis, showing lower bacterial load in lung and less severe lung pathology, than the control mice vaccinated with BCG strain containing the vector pMV261. The long-term protection induced by rBCG::X was associated with significant increases in antigen-specific IFN-gamma to both HspX and Ag85B proteins, while PPD-specific IFN-gamma responses declined. Our results suggest that latency antigens of M. tuberculosis may be promising targets for developing more effective recombinant BCG strains to protect against TB.
Department of Pathogen Biology, Tongji Medical College, Huazhong University of Science & Technology, Wuhan 430030, PR China.
Chunwei
C
Shi
Lingxia
L
Chen
Zhenhua
Z
Chen
Ying
Y
Zhang
Zhiguang
Z
Zhou
Jia
J
Lu
Ruiling
R
Fu
Chun
C
Wang
Zhengming
Z
Fang
Xionglin
X
Fan
D000217:Acyltransferases / Q000276:immunology; D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D000942:Antigens, Bacterial / Q000276:immunology*; D001500:BCG Vaccine / Q000276:immunology*; D001426:Bacterial Proteins / Q000276:immunology*; D005260:Female; D007074:Immunoglobulin G / Q000097:blood; D007371:Interferon-gamma / Q000032:analysis; D008168:Lung / Q000382:microbiology / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009169:Mycobacterium tuberculosis / Q000276:immunology; D013047:Specific Pathogen-Free Organisms; D014376:Tuberculosis / Q000276:immunology / Q000517:prevention & control*; D014614:Vaccines, Synthetic / Q000276:immunology
D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001500:BCG Vaccine; D001426:Bacterial Proteins; C118127:HspX protein, Mycobacterium tuberculosis; D007074:Immunoglobulin G; D014614:Vaccines, Synthetic; D007371:Interferon-gamma; D000217:Acyltransferases; C121433:antigen 85B, Mycobacterium tuberculosis