Immunogenicity and Protective Efficacy of a Novel Recombinant BCG Strain Overexpressing Antigens Ag85A and Ag85B

Recombinant Bacillus Calmette-Guérin (rBCG) strain is the promising vaccine candidate for tuberculosis (TB) prevention, which aims at providing more enduring and enhanced protection than the parental BCG vaccine. In this study, three rBCG strains overexpressing immunodominant antigens Ag85B (rBCG::8...

Full description

Saved in:
Bibliographic Details
Main Authors: Chun Wang, Ruiling Fu, Zhenhua Chen, Kun Tan, Lingxia Chen, Xindong Teng, Jia Lu, Chunwei Shi, Xionglin Fan
Format: Article
Language:English
Published: Wiley 2012-01-01
Series:Clinical and Developmental Immunology
Online Access:http://dx.doi.org/10.1155/2012/563838
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1832567611680882688
author Chun Wang
Ruiling Fu
Zhenhua Chen
Kun Tan
Lingxia Chen
Xindong Teng
Jia Lu
Chunwei Shi
Xionglin Fan
author_facet Chun Wang
Ruiling Fu
Zhenhua Chen
Kun Tan
Lingxia Chen
Xindong Teng
Jia Lu
Chunwei Shi
Xionglin Fan
author_sort Chun Wang
collection DOAJ
description Recombinant Bacillus Calmette-Guérin (rBCG) strain is the promising vaccine candidate for tuberculosis (TB) prevention, which aims at providing more enduring and enhanced protection than the parental BCG vaccine. In this study, three rBCG strains overexpressing immunodominant antigens Ag85B (rBCG::85B), Ag85A (rBCG::85A), or both (rBCG::AB) of Mycobacterium tuberculosis were constructed, respectively. rBCG strains showed higher level of overexpression of Ag85A and/or Ag85B proteins than BCG containing empty vector pMV261(rBCG::261), which had low levels of endogenous expression of both proteins as expected. rBCG::AB strain could provide the strongest short-term and long-term protection in the lung against intravenous infection with virulent M. tuberculosis than rBCG::261 control and other two rBCG strains overexpressing single antigen. The stronger and longer-lasting protection provided by rBCG::AB than rBCG::261 was correlated with systemic in vitro antigen-specific IFN-γ responses. Therefore, our results indicate that rBCG::AB could be a very promising TB vaccine candidate and should be further evaluated for the preclinical test.
format Article
id doaj-art-b4801bcfa968448c87e42e4614ad99b7
institution Kabale University
issn 1740-2522
1740-2530
language English
publishDate 2012-01-01
publisher Wiley
record_format Article
series Clinical and Developmental Immunology
spelling doaj-art-b4801bcfa968448c87e42e4614ad99b72025-02-03T01:00:59ZengWileyClinical and Developmental Immunology1740-25221740-25302012-01-01201210.1155/2012/563838563838Immunogenicity and Protective Efficacy of a Novel Recombinant BCG Strain Overexpressing Antigens Ag85A and Ag85BChun Wang0Ruiling Fu1Zhenhua Chen2Kun Tan3Lingxia Chen4Xindong Teng5Jia Lu6Chunwei Shi7Xionglin Fan8Laboratory of Biosafety, Department of Pathogen Biology, Tongji Medical College, Huazhong University of Science & Technology, No. 13, Hangkong Road, Wuhan 430030, ChinaLaboratory of Biosafety, Department of Pathogen Biology, Tongji Medical College, Huazhong University of Science & Technology, No. 13, Hangkong Road, Wuhan 430030, ChinaLaboratory of Biosafety, Department of Pathogen Biology, Tongji Medical College, Huazhong University of Science & Technology, No. 13, Hangkong Road, Wuhan 430030, ChinaLaboratory of Biosafety, Department of Pathogen Biology, Tongji Medical College, Huazhong University of Science & Technology, No. 13, Hangkong Road, Wuhan 430030, ChinaLaboratory of Biosafety, Department of Pathogen Biology, Tongji Medical College, Huazhong University of Science & Technology, No. 13, Hangkong Road, Wuhan 430030, ChinaLaboratory of Biosafety, Department of Pathogen Biology, Tongji Medical College, Huazhong University of Science & Technology, No. 13, Hangkong Road, Wuhan 430030, ChinaLaboratory of Biosafety, Department of Pathogen Biology, Tongji Medical College, Huazhong University of Science & Technology, No. 13, Hangkong Road, Wuhan 430030, ChinaLaboratory of Biosafety, Department of Pathogen Biology, Tongji Medical College, Huazhong University of Science & Technology, No. 13, Hangkong Road, Wuhan 430030, ChinaLaboratory of Biosafety, Department of Pathogen Biology, Tongji Medical College, Huazhong University of Science & Technology, No. 13, Hangkong Road, Wuhan 430030, ChinaRecombinant Bacillus Calmette-Guérin (rBCG) strain is the promising vaccine candidate for tuberculosis (TB) prevention, which aims at providing more enduring and enhanced protection than the parental BCG vaccine. In this study, three rBCG strains overexpressing immunodominant antigens Ag85B (rBCG::85B), Ag85A (rBCG::85A), or both (rBCG::AB) of Mycobacterium tuberculosis were constructed, respectively. rBCG strains showed higher level of overexpression of Ag85A and/or Ag85B proteins than BCG containing empty vector pMV261(rBCG::261), which had low levels of endogenous expression of both proteins as expected. rBCG::AB strain could provide the strongest short-term and long-term protection in the lung against intravenous infection with virulent M. tuberculosis than rBCG::261 control and other two rBCG strains overexpressing single antigen. The stronger and longer-lasting protection provided by rBCG::AB than rBCG::261 was correlated with systemic in vitro antigen-specific IFN-γ responses. Therefore, our results indicate that rBCG::AB could be a very promising TB vaccine candidate and should be further evaluated for the preclinical test.http://dx.doi.org/10.1155/2012/563838
spellingShingle Chun Wang
Ruiling Fu
Zhenhua Chen
Kun Tan
Lingxia Chen
Xindong Teng
Jia Lu
Chunwei Shi
Xionglin Fan
Immunogenicity and Protective Efficacy of a Novel Recombinant BCG Strain Overexpressing Antigens Ag85A and Ag85B
Clinical and Developmental Immunology
title Immunogenicity and Protective Efficacy of a Novel Recombinant BCG Strain Overexpressing Antigens Ag85A and Ag85B
title_full Immunogenicity and Protective Efficacy of a Novel Recombinant BCG Strain Overexpressing Antigens Ag85A and Ag85B
title_fullStr Immunogenicity and Protective Efficacy of a Novel Recombinant BCG Strain Overexpressing Antigens Ag85A and Ag85B
title_full_unstemmed Immunogenicity and Protective Efficacy of a Novel Recombinant BCG Strain Overexpressing Antigens Ag85A and Ag85B
title_short Immunogenicity and Protective Efficacy of a Novel Recombinant BCG Strain Overexpressing Antigens Ag85A and Ag85B
title_sort immunogenicity and protective efficacy of a novel recombinant bcg strain overexpressing antigens ag85a and ag85b
url http://dx.doi.org/10.1155/2012/563838
work_keys_str_mv AT chunwang immunogenicityandprotectiveefficacyofanovelrecombinantbcgstrainoverexpressingantigensag85aandag85b
AT ruilingfu immunogenicityandprotectiveefficacyofanovelrecombinantbcgstrainoverexpressingantigensag85aandag85b
AT zhenhuachen immunogenicityandprotectiveefficacyofanovelrecombinantbcgstrainoverexpressingantigensag85aandag85b
AT kuntan immunogenicityandprotectiveefficacyofanovelrecombinantbcgstrainoverexpressingantigensag85aandag85b
AT lingxiachen immunogenicityandprotectiveefficacyofanovelrecombinantbcgstrainoverexpressingantigensag85aandag85b
AT xindongteng immunogenicityandprotectiveefficacyofanovelrecombinantbcgstrainoverexpressingantigensag85aandag85b
AT jialu immunogenicityandprotectiveefficacyofanovelrecombinantbcgstrainoverexpressingantigensag85aandag85b
AT chunweishi immunogenicityandprotectiveefficacyofanovelrecombinantbcgstrainoverexpressingantigensag85aandag85b
AT xionglinfan immunogenicityandprotectiveefficacyofanovelrecombinantbcgstrainoverexpressingantigensag85aandag85b