title: Immunogenicity and protective efficacy of heterologous prime-boost regimens with mycobacterial vaccines and recombinant adenovirus- and poxvirus-vectored vaccines against murine tuberculosis.
abstract: OBJECTIVE
  To evaluate regimens using bacillus Calmette-Guérin (BCG) or recombinant BCG (rBCG) overexpressing Ag85B for priming, followed by boosting with a modified vaccinia virus Ankara strain (MVA) and/or adenovirus vector (AD) expressing an Ag85B-ESAT6 fusion protein.
  
  
  METHODS
  Cellular and humoral immune responses were determined after subcutaneous vaccination, which was employed to trigger systemic immunity against intravenous infection in a mouse model of tuberculosis (TB). Bacterial loads and lung histology were evaluated.
  
  
  RESULTS
  The relative IgG2a and IgG1 antibody levels indicated that the viral-vectored vaccines generated a T-helper type 1 (Th1)-biased response after two doses of viral boost vaccinations. Boosting BCG-primed mice with viral vaccines induced a Th1 immune response that included both CD4 and CD8 T-cells generating antigen-specific interferon-gamma (IFN-γ) and CD8 T cytotoxic activity. Only mice vaccinated with two different viral boosters after BCG priming exhibited a significant reduction in bacterial burden in the lung after challenge. Histology examinations confirmed the attenuation of lung damage and more compact granulomas. After mycobacteria priming, boosting with AD85B-E6 followed by MVA85B-E6 afforded better protection than the reverse order of administration of the viral vectors.
  
  
  CONCLUSIONS
  This study demonstrates the potential of multiple heterologous viral booster vaccines, although the exact correlates of protection and optimal regimens should be further investigated for the rational design of future vaccine strategies.
authors.affiliation: National Engineering Laboratory for AIDS Vaccine, School of Life Science, Jilin University, Gaoxin District Changchun, Jilin, China.
authors.forename: Qingrui
authors.initials: Q
authors.lastname: You
authors.forename: Yongge
authors.initials: Y
authors.lastname: Wu
authors.forename: Yang
authors.initials: Y
authors.lastname: Wu
authors.forename: Wei
authors.initials: W
authors.lastname: Wei
authors.forename: Changyong
authors.initials: C
authors.lastname: Wang
authors.forename: Dehua
authors.initials: D
authors.lastname: Jiang
authors.forename: Xianghui
authors.initials: X
authors.lastname: Yu
authors.forename: Xizhen
authors.initials: X
authors.lastname: Zhang
authors.forename: Yong
authors.initials: Y
authors.lastname: Wang
authors.forename: Zhijiao
authors.initials: Z
authors.lastname: Tang
authors.forename: Chunlai
authors.initials: C
authors.lastname: Jiang
authors.forename: Wei
authors.initials: W
authors.lastname: Kong
mesh_terms: D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D001500:BCG Vaccine / Q000235:genetics / Q000276:immunology / Q000494:pharmacology*; D003601:Cytotoxicity Tests, Immunologic; D005260:Female; D005822:Genetic Vectors / Q000276:immunology*; D006651:Histocytochemistry; D007371:Interferon-gamma / Q000097:blood; D051379:Mice; D008807:Mice, Inbred BALB C; D009169:Mycobacterium tuberculosis / Q000235:genetics / Q000276:immunology*; D013047:Specific Pathogen-Free Organisms; D018417:Th1 Cells / Q000276:immunology; D014376:Tuberculosis / Q000276:immunology* / Q000382:microbiology / Q000517:prevention & control*; D014614:Vaccines, Synthetic / Q000235:genetics / Q000276:immunology / Q000494:pharmacology
chemical_list: D000907:Antibodies, Bacterial; D001500:BCG Vaccine; D014614:Vaccines, Synthetic; D007371:Interferon-gamma