A live attenuated BCG vaccine overexpressing multistage antigens Ag85B and HspX provides superior protection against Mycobacterium tuberculosis infection

Verfasser / Beitragende:
[Xuefeng Yuan, Xindong Teng, Yukai Jing, Jilei Ma, Maopeng Tian, Qi Yu, Lei Zhou, Ruibo Wang, Weihua Wang, Li Li, Xionglin Fan]
Ort, Verlag, Jahr:
2015
Enthalten in:
Applied Microbiology and Biotechnology, 99/24(2015-12-01), 10587-10595
Format:
Artikel (online)
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024 7 0 |a 10.1007/s00253-015-6962-x  |2 doi 
035 |a (NATIONALLICENCE)springer-10.1007/s00253-015-6962-x 
245 0 2 |a A live attenuated BCG vaccine overexpressing multistage antigens Ag85B and HspX provides superior protection against Mycobacterium tuberculosis infection  |h [Elektronische Daten]  |c [Xuefeng Yuan, Xindong Teng, Yukai Jing, Jilei Ma, Maopeng Tian, Qi Yu, Lei Zhou, Ruibo Wang, Weihua Wang, Li Li, Xionglin Fan] 
520 3 |a Tuberculosis (TB) remains one of the most menacing infectious diseases, although attenuated Mycobacterium bovis Bacillus Calmette-Guerin (BCG) vaccine has been widely used to protect children against primary TB. There are increasing evidences that rapid growing and dormant Mycobacterium tuberculosis (M. tuberculosis) coexist in vivo after infection. However, BCG vaccine only elicits cell-mediated immune responses to secretory antigens expressed by rapid growing pathogen. BCG vaccine is thus unable to thwart the reactivation of latent tuberculosis infection (LTBI), and its protection wanes over age after neonatal immunization. In order to extend its ability for a durable protection, a novel recombinant BCG (rBCG) strain, named rBCG::XB, was constructed by overexpressing immunodominant multistage antigens of Ag85B and HspX, which are expressed by both rapid replicating and dormant M. tuberculosis. Long-term protective effect and immunogenicity of rBCG::XB were compared with the parental BCG in vaccinated C57BL/6 mice. Our results demonstrated that rBCG::XB provided the stronger and long-lasting protection against M. tuberculosis H37Rv intranasal infection than BCG. The rBCG::XB not only elicited the more durable multistage antigen-specific CD4+Th1-biased immune responses and specific polyfunctional CD4+T cells but also augmented the CD8+ CTL effects against Ag85B in vivo. In particular, higher levels of CD4+ TEM and CD8+ TCM cells, dominated by IL2+ CD4+ and CD8+ TCM cells, were obtained in the spleen of rBCG::XB vaccinated mice. Therefore, our findings indicate that rBCG::XB is a promising candidate to improve the efficacy of BCG. 
540 |a Springer-Verlag Berlin Heidelberg, 2015 
690 7 |a Tuberculosis  |2 nationallicence 
690 7 |a Recombinant BCG  |2 nationallicence 
690 7 |a Ag85B  |2 nationallicence 
690 7 |a HspX  |2 nationallicence 
690 7 |a Overexpresssion  |2 nationallicence 
690 7 |a Vaccine  |2 nationallicence 
700 1 |a Yuan  |D Xuefeng  |u Department of Pathogen Biology, School of Basic Medicine, Huazhong University of Science and Technology, 430030, Wuhan, People's Republic of China  |4 aut 
700 1 |a Teng  |D Xindong  |u Department of Pathogen Biology, School of Basic Medicine, Huazhong University of Science and Technology, 430030, Wuhan, People's Republic of China  |4 aut 
700 1 |a Jing  |D Yukai  |u Department of Pathogen Biology, School of Basic Medicine, Huazhong University of Science and Technology, 430030, Wuhan, People's Republic of China  |4 aut 
700 1 |a Ma  |D Jilei  |u Department of Pathogen Biology, School of Basic Medicine, Huazhong University of Science and Technology, 430030, Wuhan, People's Republic of China  |4 aut 
700 1 |a Tian  |D Maopeng  |u Department of Pathogen Biology, School of Basic Medicine, Huazhong University of Science and Technology, 430030, Wuhan, People's Republic of China  |4 aut 
700 1 |a Yu  |D Qi  |u Department of Pathogen Biology, School of Basic Medicine, Huazhong University of Science and Technology, 430030, Wuhan, People's Republic of China  |4 aut 
700 1 |a Zhou  |D Lei  |u Beijing Pushikang Pharmaceutical Co., Ltd., 100020, Beijing, People's Republic of China  |4 aut 
700 1 |a Wang  |D Ruibo  |u Beijing Pushikang Pharmaceutical Co., Ltd., 100020, Beijing, People's Republic of China  |4 aut 
700 1 |a Wang  |D Weihua  |u Wuhan Pulmonary Hospital, Wuhan Institute for Tuberculosis Control, 430030, Wuhan, People's Republic of China  |4 aut 
700 1 |a Li  |D Li  |u Wuhan Pulmonary Hospital, Wuhan Institute for Tuberculosis Control, 430030, Wuhan, People's Republic of China  |4 aut 
700 1 |a Fan  |D Xionglin  |u Department of Pathogen Biology, School of Basic Medicine, Huazhong University of Science and Technology, 430030, Wuhan, People's Republic of China  |4 aut 
773 0 |t Applied Microbiology and Biotechnology  |d Springer Berlin Heidelberg  |g 99/24(2015-12-01), 10587-10595  |x 0175-7598  |q 99:24<10587  |1 2015  |2 99  |o 253 
856 4 0 |u https://doi.org/10.1007/s00253-015-6962-x  |q text/html  |z Onlinezugriff via DOI 
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900 7 |a Metadata rights reserved  |b Springer special CC-BY-NC licence  |2 nationallicence 
908 |D 1  |a research-article  |2 jats 
949 |B NATIONALLICENCE  |F NATIONALLICENCE  |b NL-springer 
950 |B NATIONALLICENCE  |P 856  |E 40  |u https://doi.org/10.1007/s00253-015-6962-x  |q text/html  |z Onlinezugriff via DOI 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Yuan  |D Xuefeng  |u Department of Pathogen Biology, School of Basic Medicine, Huazhong University of Science and Technology, 430030, Wuhan, People's Republic of China  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Teng  |D Xindong  |u Department of Pathogen Biology, School of Basic Medicine, Huazhong University of Science and Technology, 430030, Wuhan, People's Republic of China  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Jing  |D Yukai  |u Department of Pathogen Biology, School of Basic Medicine, Huazhong University of Science and Technology, 430030, Wuhan, People's Republic of China  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Ma  |D Jilei  |u Department of Pathogen Biology, School of Basic Medicine, Huazhong University of Science and Technology, 430030, Wuhan, People's Republic of China  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Tian  |D Maopeng  |u Department of Pathogen Biology, School of Basic Medicine, Huazhong University of Science and Technology, 430030, Wuhan, People's Republic of China  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Yu  |D Qi  |u Department of Pathogen Biology, School of Basic Medicine, Huazhong University of Science and Technology, 430030, Wuhan, People's Republic of China  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Zhou  |D Lei  |u Beijing Pushikang Pharmaceutical Co., Ltd., 100020, Beijing, People's Republic of China  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Wang  |D Ruibo  |u Beijing Pushikang Pharmaceutical Co., Ltd., 100020, Beijing, People's Republic of China  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Wang  |D Weihua  |u Wuhan Pulmonary Hospital, Wuhan Institute for Tuberculosis Control, 430030, Wuhan, People's Republic of China  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Li  |D Li  |u Wuhan Pulmonary Hospital, Wuhan Institute for Tuberculosis Control, 430030, Wuhan, People's Republic of China  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Fan  |D Xionglin  |u Department of Pathogen Biology, School of Basic Medicine, Huazhong University of Science and Technology, 430030, Wuhan, People's Republic of China  |4 aut 
950 |B NATIONALLICENCE  |P 773  |E 0-  |t Applied Microbiology and Biotechnology  |d Springer Berlin Heidelberg  |g 99/24(2015-12-01), 10587-10595  |x 0175-7598  |q 99:24<10587  |1 2015  |2 99  |o 253