caa a22 4500 605502412 CHVBK 20210128100605.0 cr unu---uuuuu 210128e20151201xx s 000 0 eng 10.1007/s00253-015-6962-x doi (NATIONALLICENCE)springer-10.1007/s00253-015-6962-x A live attenuated BCG vaccine overexpressing multistage antigens Ag85B and HspX provides superior protection against Mycobacterium tuberculosis infection [Elektronische Daten] [Xuefeng Yuan, Xindong Teng, Yukai Jing, Jilei Ma, Maopeng Tian, Qi Yu, Lei Zhou, Ruibo Wang, Weihua Wang, Li Li, Xionglin Fan] 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. Springer-Verlag Berlin Heidelberg, 2015 Tuberculosis nationallicence Recombinant BCG nationallicence Ag85B nationallicence HspX nationallicence Overexpresssion nationallicence Vaccine nationallicence Yuan Xuefeng Department of Pathogen Biology, School of Basic Medicine, Huazhong University of Science and Technology, 430030, Wuhan, People's Republic of China aut Teng Xindong Department of Pathogen Biology, School of Basic Medicine, Huazhong University of Science and Technology, 430030, Wuhan, People's Republic of China aut Jing Yukai Department of Pathogen Biology, School of Basic Medicine, Huazhong University of Science and Technology, 430030, Wuhan, People's Republic of China aut Ma Jilei Department of Pathogen Biology, School of Basic Medicine, Huazhong University of Science and Technology, 430030, Wuhan, People's Republic of China aut Tian Maopeng Department of Pathogen Biology, School of Basic Medicine, Huazhong University of Science and Technology, 430030, Wuhan, People's Republic of China aut Yu Qi Department of Pathogen Biology, School of Basic Medicine, Huazhong University of Science and Technology, 430030, Wuhan, People's Republic of China aut Zhou Lei Beijing Pushikang Pharmaceutical Co., Ltd., 100020, Beijing, People's Republic of China aut Wang Ruibo Beijing Pushikang Pharmaceutical Co., Ltd., 100020, Beijing, People's Republic of China aut Wang Weihua Wuhan Pulmonary Hospital, Wuhan Institute for Tuberculosis Control, 430030, Wuhan, People's Republic of China aut Li Li Wuhan Pulmonary Hospital, Wuhan Institute for Tuberculosis Control, 430030, Wuhan, People's Republic of China aut Fan Xionglin Department of Pathogen Biology, School of Basic Medicine, Huazhong University of Science and Technology, 430030, Wuhan, People's Republic of China aut Applied Microbiology and Biotechnology Springer Berlin Heidelberg 99/24(2015-12-01), 10587-10595 0175-7598 99:24<10587 2015 99 253 https://doi.org/10.1007/s00253-015-6962-x text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s00253-015-6962-x text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Yuan Xuefeng Department of Pathogen Biology, School of Basic Medicine, Huazhong University of Science and Technology, 430030, Wuhan, People's Republic of China aut NATIONALLICENCE 700 1- Teng Xindong Department of Pathogen Biology, School of Basic Medicine, Huazhong University of Science and Technology, 430030, Wuhan, People's Republic of China aut NATIONALLICENCE 700 1- Jing Yukai Department of Pathogen Biology, School of Basic Medicine, Huazhong University of Science and Technology, 430030, Wuhan, People's Republic of China aut NATIONALLICENCE 700 1- Ma Jilei Department of Pathogen Biology, School of Basic Medicine, Huazhong University of Science and Technology, 430030, Wuhan, People's Republic of China aut NATIONALLICENCE 700 1- Tian Maopeng Department of Pathogen Biology, School of Basic Medicine, Huazhong University of Science and Technology, 430030, Wuhan, People's Republic of China aut NATIONALLICENCE 700 1- Yu Qi Department of Pathogen Biology, School of Basic Medicine, Huazhong University of Science and Technology, 430030, Wuhan, People's Republic of China aut NATIONALLICENCE 700 1- Zhou Lei Beijing Pushikang Pharmaceutical Co., Ltd., 100020, Beijing, People's Republic of China aut NATIONALLICENCE 700 1- Wang Ruibo Beijing Pushikang Pharmaceutical Co., Ltd., 100020, Beijing, People's Republic of China aut NATIONALLICENCE 700 1- Wang Weihua Wuhan Pulmonary Hospital, Wuhan Institute for Tuberculosis Control, 430030, Wuhan, People's Republic of China aut NATIONALLICENCE 700 1- Li Li Wuhan Pulmonary Hospital, Wuhan Institute for Tuberculosis Control, 430030, Wuhan, People's Republic of China aut NATIONALLICENCE 700 1- Fan Xionglin Department of Pathogen Biology, School of Basic Medicine, Huazhong University of Science and Technology, 430030, Wuhan, People's Republic of China aut NATIONALLICENCE 773 0- Applied Microbiology and Biotechnology Springer Berlin Heidelberg 99/24(2015-12-01), 10587-10595 0175-7598 99:24<10587 2015 99 253