title: Subcutaneous administration of modified vaccinia virus Ankara expressing an Ag85B-ESAT6 fusion protein, but not an adenovirus-based vaccine, protects mice against intravenous challenge with Mycobacterium tuberculosis.
abstract: Recombinant virus-based tuberculosis (TB) vaccines that are strongly immunogenic and elicit robust cellular immunity are considered ideal vaccine candidates. Here, we engineered a poxvirus-based vaccine, MVA85B-E6, and an adenovirus-based vaccine, AD85B-E6, both of which express the fusion protein Ag85B-ESAT6. Subcutaneous vaccination of AD85B-E6 generated strong interferon (IFN)-γ production by both CD4 and CD8 T cells and CD8 cytotoxic T lymphocyte activity; these results indicate that strong T-helper type 1 immune responses were elicited in mice, which is in contrast to the moderate responses induced by vaccination with MVA85B-E6. However, MVA85B-E6 given subcutaneously led to levels of protection comparable with that induced by the bacillus Calmette-Guérin vaccine in the lungs and spleens, whereas AD85B-E6 given subcutaneously did not show any protective efficacy after intravenous challenge of BALB/c mice with Mycobacterium tuberculosis H37Rv. Our study emphasizes that more efficient biomarkers for vaccine efficacy and more appropriate routes of vaccine administration are necessary for the development of a successful TB vaccine.
authors.affiliation: National Engineering Laboratory of AIDS Vaccine, School of Life Science, Jilin University, Jilin, China.
authors.forename: Q
authors.initials: Q
authors.lastname: You
authors.forename: C
authors.initials: C
authors.lastname: Jiang
authors.forename: Y
authors.initials: Y
authors.lastname: Wu
authors.forename: X
authors.initials: X
authors.lastname: Yu
authors.forename: Y
authors.initials: Y
authors.lastname: Chen
authors.forename: X
authors.initials: X
authors.lastname: Zhang
authors.forename: W
authors.initials: W
authors.lastname: Wei
authors.forename: Y
authors.initials: Y
authors.lastname: Wang
authors.forename: Z
authors.initials: Z
authors.lastname: Tang
authors.forename: D
authors.initials: D
authors.lastname: Jiang
authors.forename: Y
authors.initials: Y
authors.lastname: Wu
authors.forename: C
authors.initials: C
authors.lastname: Wang
authors.forename: X
authors.initials: X
authors.lastname: Meng
authors.forename: X
authors.initials: X
authors.lastname: Zhao
authors.forename: W
authors.initials: W
authors.lastname: Kong
mesh_terms: D000217:Acyltransferases / Q000235:genetics / Q000276:immunology*; D000818:Animals; D000942:Antigens, Bacterial / Q000235:genetics / Q000276:immunology*; D001426:Bacterial Proteins / Q000235:genetics / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000382:microbiology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000382:microbiology; D003602:Cytotoxicity, Immunologic / Q000276:immunology; D006651:Histocytochemistry; D006801:Humans; D007371:Interferon-gamma / Q000032:analysis; D051379:Mice; D008807:Mice, Inbred BALB C; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D013047:Specific Pathogen-Free Organisms; D018709:Statistics, Nonparametric; D014376:Tuberculosis / Q000276:immunology* / Q000382:microbiology / Q000517:prevention & control*; D032581:Tuberculosis Vaccines / Q000276:immunology / Q000494:pharmacology*; D014611:Vaccination / Q000379:methods / Q000592:standards; D014614:Vaccines, Synthetic / Q000235:genetics / Q000276:immunology; D014616:Vaccinia virus / Q000235:genetics / Q000276:immunology*
chemical_list: D000942:Antigens, Bacterial; D001426:Bacterial Proteins; C093276:ESAT-6 protein, Mycobacterium tuberculosis; D032581:Tuberculosis Vaccines; D014614:Vaccines, Synthetic; D007371:Interferon-gamma; D000217:Acyltransferases; C121433:antigen 85B, Mycobacterium tuberculosis