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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
Author(s) -
You Q.,
Jiang C.,
Wu Y.,
Yu X.,
Chen Y.,
Zhang X.,
Wei W.,
Wang Y.,
Tang Z.,
Jiang D.,
Wu Y.,
Wang C.,
Meng X.,
Zhao X.,
Kong W.
Publication year - 2012
Publication title -
scandinavian journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.934
H-Index - 88
eISSN - 1365-3083
pISSN - 0300-9475
DOI - 10.1111/j.1365-3083.2011.02629.x
Subject(s) - vaccinia , virology , mycobacterium tuberculosis , vaccination , tuberculosis vaccines , tuberculosis , immunity , medicine , cytotoxic t cell , immune system , cd8 , bcg vaccine , virus , immunology , biology , recombinant dna , in vitro , biochemistry , pathology , gene
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.