000151228 001__ 151228
000151228 005__ 20181203021957.0
000151228 022__ $$a0019-9567
000151228 02470 $$2PMID$$a15784562
000151228 0247_ $$2doi$$a10.1128/IAI.73.4.2190-2196.2005
000151228 037__ $$aARTICLE
000151228 245__ $$aDifferential effects of prior exposure to environmental mycobacteria on vaccination with Mycobacterium bovis BCG or a recombinant BCG strain expressing RD1 antigens
000151228 269__ $$a2005
000151228 260__ $$c2005
000151228 336__ $$aJournal Articles
000151228 520__ $$aIn silico analysis reveals that most protective antigens expressed by the antituberculous vaccine Mycobacterium bovis BCG (BCG) are conserved in M. avium, supporting the hypothesis that exposure to environmental mycobacteria generates cross-reactive immune responses blocking BCG activity. We investigated the impact of sensitization with M. avium, M. scrofulaceum, or M. vaccae on the protective efficacy of a recombinant BCG strain expressing RD1 antigens (BCG::RD1), using a mouse model of experimental tuberculosis (TB). No evidence that the RD1-encoded antigens ESAT-6, CFP-10, and PPE68 were expressed by these environmental strains could be demonstrated by Western blot analysis. Mice sensitized with each of these strains did not prime cellular immune responses cross-reacting with the immunodominant ESAT-6. Importantly, clearance of BCG::RD1 from the lungs and spleens of mice exposed to each of the environmental strains before vaccination was minimal compared to that of BCG. In mice sensitized with M. avium, increased persistence of BCG::RD1 correlated with stronger antimycobacterial gamma interferon responses and enhanced protection against aerosol infection with M. tuberculosis, compared to BCG. In contrast, animals exposed to M. scrofulaceum or M. vaccae prior to vaccination with BCG or BCG::RD1 were better protected against TB than were the unsensitized controls. Our results suggest that the inhibitory effect of environmental mycobacteria on the protective efficacy of BCG depends critically on the extent of cross-recognition of antigens shared with the vaccine. In hosts sensitized with M. avium, potent immunogenicity of ESAT-6 and increased persistence of BCG::RD1 may allow this recombinant vaccine to overcome preexisting antimycobacterial responses.
000151228 6531_ $$aEnvironmental Microbiology
000151228 700__ $$aDemangel, Caroline
000151228 700__ $$aGarnier, Thierry
000151228 700__ $$aRosenkrands, Ida
000151228 700__ $$g177247$$aCole, Stewart T$$0243892
000151228 773__ $$j73$$tInfection and immunity$$k4$$q2190-6
000151228 909C0 $$xU11742$$0252302$$pUPCOL
000151228 909CO $$pSV$$particle$$ooai:infoscience.tind.io:151228
000151228 937__ $$aEPFL-ARTICLE-151228
000151228 973__ $$rREVIEWED$$sPUBLISHED$$aOTHER
000151228 980__ $$aARTICLE