title: Boosting BCG-primed mice with chimeric DNA vaccine HG856A induces potent multifunctional T cell responses and enhanced protection against Mycobacterium tuberculosis.
abstract: The tuberculosis pandemic continues to rampage despite widespread use of the current Bacillus Calmette-Guerin (BCG) vaccine. Because DNA vaccines can elicit effective antigen-specific immune responses, including potent T cell-mediated immunity, they are promising vehicles for antigen delivery. In a prime-boost approach, they can supplement the inadequate anti-TB immunological memory induced by BCG. Based on this, a chimeric DNA vaccine HG856A encoding Mycobacterium tuberculosis (M. tuberculosis) immunodominant antigen Ag85A plus two copies of ESAT-6 was constructed. Potent humoral immune responses, as well as therapeutic effects induced by this DNA vaccine, were observed previously in M. tuberculosis-infected mice. In this study, we further evaluated the antigen-specific T cell immune responses and showed that repeated immunization with HG856A gave modest protection against M. tuberculosis challenge infection and significantly boosted the immune protection primed by BCG vaccination. Enhanced protection was accompanied by increased multifunctional Th1 CD4(+) T cell responses, most notably by an elevated frequency of M. tuberculosis antigen-specific IL-2-producing CD4(+) T cells post-vaccination. These data confirm the potential of chimeric DNA vaccine HG856A as an anti-TB vaccine candidate.
authors.affiliation: Shanghai Public Health Clinical Center, Key Laboratory of Medical Molecular Virology of MOE/MOH, Fudan University, Shanghai, 201508, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Ji
authors.affiliation: Shanghai Public Health Clinical Center, Key Laboratory of Medical Molecular Virology of MOE/MOH, Fudan University, Shanghai, 201508, China.
authors.forename: Zhi-Dong
authors.initials: ZD
authors.lastname: Hu
authors.affiliation: Shanghai Public Health Clinical Center, Key Laboratory of Medical Molecular Virology of MOE/MOH, Fudan University, Shanghai, 201508, China.
authors.forename: Han
authors.initials: H
authors.lastname: Kang
authors.affiliation: Shanghai Public Health Clinical Center, Key Laboratory of Medical Molecular Virology of MOE/MOH, Fudan University, Shanghai, 201508, China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Yuan
authors.affiliation: Shanghai Public Health Clinical Center, Key Laboratory of Medical Molecular Virology of MOE/MOH, Fudan University, Shanghai, 201508, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Ma
authors.affiliation: School of Laboratory Medicine and Life Science, Wenzhou Medical University, Wenzhou, 325035, China.
authors.forename: Han-Li
authors.initials: HL
authors.lastname: Wen
authors.affiliation: Shanghai Public Health Clinical Center, Key Laboratory of Medical Molecular Virology of MOE/MOH, Fudan University, Shanghai, 201508, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Wu
authors.affiliation: Shanghai H&G Biotech. Co. Ltd., Shanghai, 200061, China.
authors.forename: Zhong-Ming
authors.initials: ZM
authors.lastname: Li
authors.affiliation: Shanghai Public Health Clinical Center, Key Laboratory of Medical Molecular Virology of MOE/MOH, Fudan University, Shanghai, 201508, China. lowried@fudan.edu.cn.
authors.forename: Douglas B
authors.initials: DB
authors.lastname: Lowrie
authors.affiliation: Shanghai Public Health Clinical Center, Key Laboratory of Medical Molecular Virology of MOE/MOH, Fudan University, Shanghai, 201508, China. xyfan008@fudan.edu.cn.|School of Laboratory Medicine and Life Science, Wenzhou Medical University, Wenzhou, 325035, China. xyfan008@fudan.edu.cn.
authors.forename: Xiao-Yong
authors.initials: XY
authors.lastname: Fan
mesh_terms: D000217:Acyltransferases / Q000235:genetics; D000818:Animals; D000942:Antigens, Bacterial / Q000235:genetics; D001500:BCG Vaccine / Q000276:immunology*; D001426:Bacterial Proteins / Q000235:genetics; D005260:Female; D006801:Humans; D056724:Immunity, Humoral; D007117:Immunization, Secondary; D007156:Immunologic Memory; D007376:Interleukin-2 / Q000378:metabolism; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology* / Q000382:microbiology; D014376:Tuberculosis / Q000276:immunology / Q000517:prevention & control*; D019444:Vaccines, DNA / Q000276:immunology*
chemical_list: D000942:Antigens, Bacterial; D001500:BCG Vaccine; D001426:Bacterial Proteins; C093276:ESAT-6 protein, Mycobacterium tuberculosis; D007376:Interleukin-2; D019444:Vaccines, DNA; D000217:Acyltransferases; C112580:antigen 85A, Mycobacterium tuberculosis
keywords: DNA vaccine; HG856A; Mycobacterium tuberculosis; Prime–boost; T cell responses