Recombinant BCG Expressing LTAK63 Adjuvant induces Superior Protection against Mycobacterium tuberculosis

Abstract In order to develop an improved BCG vaccine against tuberculosis we have taken advantage of the adjuvant properties of a non-toxic derivative of Escherichia coli heat labile enterotoxin (LT), LTAK63. We have constructed rBCG strains expressing LTAK63 at different expression levels. Mice imm...
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Autor*in:	Ivan P. Nascimento [verfasserIn] Dunia Rodriguez [verfasserIn] Carina C. Santos [verfasserIn] Eduardo P. Amaral [verfasserIn] Henrique K. Rofatto [verfasserIn] Ana P. Junqueira-Kipnis [verfasserIn] Eduardo D. C. Gonçalves [verfasserIn] Maria R. D’Império-Lima [verfasserIn] Mario H. Hirata [verfasserIn] Celio L. Silva [verfasserIn] Nathalie Winter [verfasserIn] Brigitte Gicquel [verfasserIn] Kingston H. G. Mills [verfasserIn] Mariagrazia Pizza [verfasserIn] Rino Rappuoli [verfasserIn] Luciana C. C. Leite [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2017

Übergeordnetes Werk:	In: Scientific Reports - Nature Portfolio, 2011, 7(2017), 1, Seite 11
Übergeordnetes Werk:	volume:7 ; year:2017 ; number:1 ; pages:11

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc

DOI / URN:	10.1038/s41598-017-02003-9

Katalog-ID:	DOAJ048424722

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520			\|a Abstract In order to develop an improved BCG vaccine against tuberculosis we have taken advantage of the adjuvant properties of a non-toxic derivative of Escherichia coli heat labile enterotoxin (LT), LTAK63. We have constructed rBCG strains expressing LTAK63 at different expression levels. Mice immunized with BCG expressing low levels of LTAK63 (rBCG-LTAK63lo) showed higher Th1 cytokines and IL-17 in the lungs, and when challenged intratracheally with Mycobacterium tuberculosis displayed a 2.0–3.0 log reduction in CFU as compared to wild type BCG. Histopathological analysis of lung tissues from protected mice revealed a reduced inflammatory response. Immunization with rBCG-LTAK63lo also protected against a 100-fold higher challenge dose. Mice immunized with rBCG-LTAK63lo produced an increase in TGF-β as compared with BCG after challenge, with a corresponding reduction in Th1 and Th17 cytokines, as determined by Real Time RT-PCR. Furthermore, rBCG-LTAK63lo also displays protection against challenge with a highly virulent Beijing isolate. Our findings suggest that BCG with low-level expression of the LTAK63 adjuvant induces a stronger immune response in the lungs conferring higher levels of protection, and a novel mechanism subsequently triggers a regulatory immune response, which then limits the pathology. The rBCG-LTAK63lo strain can be the basis of an improved vaccine against tuberculosis.
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Indexfelder

author_variant	i p n ipn d r dr c c s ccs e p a epa h k r hkr a p j k apjk e d c g edcg m r d l mrdl m h h mhh c l s cls n w nw b g bg k h g m khgm m p mp r r rr l c c l lccl
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allfields	10.1038/s41598-017-02003-9 doi (DE-627)DOAJ048424722 (DE-599)DOAJdf9d3306cb574c71b46f4ee32a1a4202 DE-627 ger DE-627 rakwb eng Ivan P. Nascimento verfasserin aut Recombinant BCG Expressing LTAK63 Adjuvant induces Superior Protection against Mycobacterium tuberculosis 2017 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract In order to develop an improved BCG vaccine against tuberculosis we have taken advantage of the adjuvant properties of a non-toxic derivative of Escherichia coli heat labile enterotoxin (LT), LTAK63. We have constructed rBCG strains expressing LTAK63 at different expression levels. Mice immunized with BCG expressing low levels of LTAK63 (rBCG-LTAK63lo) showed higher Th1 cytokines and IL-17 in the lungs, and when challenged intratracheally with Mycobacterium tuberculosis displayed a 2.0–3.0 log reduction in CFU as compared to wild type BCG. Histopathological analysis of lung tissues from protected mice revealed a reduced inflammatory response. Immunization with rBCG-LTAK63lo also protected against a 100-fold higher challenge dose. Mice immunized with rBCG-LTAK63lo produced an increase in TGF-β as compared with BCG after challenge, with a corresponding reduction in Th1 and Th17 cytokines, as determined by Real Time RT-PCR. Furthermore, rBCG-LTAK63lo also displays protection against challenge with a highly virulent Beijing isolate. Our findings suggest that BCG with low-level expression of the LTAK63 adjuvant induces a stronger immune response in the lungs conferring higher levels of protection, and a novel mechanism subsequently triggers a regulatory immune response, which then limits the pathology. The rBCG-LTAK63lo strain can be the basis of an improved vaccine against tuberculosis. Medicine R Science Q Dunia Rodriguez verfasserin aut Carina C. Santos verfasserin aut Eduardo P. Amaral verfasserin aut Henrique K. Rofatto verfasserin aut Ana P. Junqueira-Kipnis verfasserin aut Eduardo D. C. Gonçalves verfasserin aut Maria R. D’Império-Lima verfasserin aut Mario H. Hirata verfasserin aut Celio L. Silva verfasserin aut Nathalie Winter verfasserin aut Brigitte Gicquel verfasserin aut Kingston H. G. Mills verfasserin aut Mariagrazia Pizza verfasserin aut Rino Rappuoli verfasserin aut Luciana C. C. Leite verfasserin aut In Scientific Reports Nature Portfolio, 2011 7(2017), 1, Seite 11 (DE-627)663366712 (DE-600)2615211-3 20452322 nnns volume:7 year:2017 number:1 pages:11 https://doi.org/10.1038/s41598-017-02003-9 kostenfrei https://doaj.org/article/df9d3306cb574c71b46f4ee32a1a4202 kostenfrei https://doi.org/10.1038/s41598-017-02003-9 kostenfrei https://doaj.org/toc/2045-2322 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_381 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4335 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 7 2017 1 11
spelling	10.1038/s41598-017-02003-9 doi (DE-627)DOAJ048424722 (DE-599)DOAJdf9d3306cb574c71b46f4ee32a1a4202 DE-627 ger DE-627 rakwb eng Ivan P. Nascimento verfasserin aut Recombinant BCG Expressing LTAK63 Adjuvant induces Superior Protection against Mycobacterium tuberculosis 2017 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract In order to develop an improved BCG vaccine against tuberculosis we have taken advantage of the adjuvant properties of a non-toxic derivative of Escherichia coli heat labile enterotoxin (LT), LTAK63. We have constructed rBCG strains expressing LTAK63 at different expression levels. Mice immunized with BCG expressing low levels of LTAK63 (rBCG-LTAK63lo) showed higher Th1 cytokines and IL-17 in the lungs, and when challenged intratracheally with Mycobacterium tuberculosis displayed a 2.0–3.0 log reduction in CFU as compared to wild type BCG. Histopathological analysis of lung tissues from protected mice revealed a reduced inflammatory response. Immunization with rBCG-LTAK63lo also protected against a 100-fold higher challenge dose. Mice immunized with rBCG-LTAK63lo produced an increase in TGF-β as compared with BCG after challenge, with a corresponding reduction in Th1 and Th17 cytokines, as determined by Real Time RT-PCR. Furthermore, rBCG-LTAK63lo also displays protection against challenge with a highly virulent Beijing isolate. Our findings suggest that BCG with low-level expression of the LTAK63 adjuvant induces a stronger immune response in the lungs conferring higher levels of protection, and a novel mechanism subsequently triggers a regulatory immune response, which then limits the pathology. The rBCG-LTAK63lo strain can be the basis of an improved vaccine against tuberculosis. Medicine R Science Q Dunia Rodriguez verfasserin aut Carina C. Santos verfasserin aut Eduardo P. Amaral verfasserin aut Henrique K. Rofatto verfasserin aut Ana P. Junqueira-Kipnis verfasserin aut Eduardo D. C. Gonçalves verfasserin aut Maria R. D’Império-Lima verfasserin aut Mario H. Hirata verfasserin aut Celio L. Silva verfasserin aut Nathalie Winter verfasserin aut Brigitte Gicquel verfasserin aut Kingston H. G. Mills verfasserin aut Mariagrazia Pizza verfasserin aut Rino Rappuoli verfasserin aut Luciana C. C. Leite verfasserin aut In Scientific Reports Nature Portfolio, 2011 7(2017), 1, Seite 11 (DE-627)663366712 (DE-600)2615211-3 20452322 nnns volume:7 year:2017 number:1 pages:11 https://doi.org/10.1038/s41598-017-02003-9 kostenfrei https://doaj.org/article/df9d3306cb574c71b46f4ee32a1a4202 kostenfrei https://doi.org/10.1038/s41598-017-02003-9 kostenfrei https://doaj.org/toc/2045-2322 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_381 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4335 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 7 2017 1 11
allfields_unstemmed	10.1038/s41598-017-02003-9 doi (DE-627)DOAJ048424722 (DE-599)DOAJdf9d3306cb574c71b46f4ee32a1a4202 DE-627 ger DE-627 rakwb eng Ivan P. Nascimento verfasserin aut Recombinant BCG Expressing LTAK63 Adjuvant induces Superior Protection against Mycobacterium tuberculosis 2017 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract In order to develop an improved BCG vaccine against tuberculosis we have taken advantage of the adjuvant properties of a non-toxic derivative of Escherichia coli heat labile enterotoxin (LT), LTAK63. We have constructed rBCG strains expressing LTAK63 at different expression levels. Mice immunized with BCG expressing low levels of LTAK63 (rBCG-LTAK63lo) showed higher Th1 cytokines and IL-17 in the lungs, and when challenged intratracheally with Mycobacterium tuberculosis displayed a 2.0–3.0 log reduction in CFU as compared to wild type BCG. Histopathological analysis of lung tissues from protected mice revealed a reduced inflammatory response. Immunization with rBCG-LTAK63lo also protected against a 100-fold higher challenge dose. Mice immunized with rBCG-LTAK63lo produced an increase in TGF-β as compared with BCG after challenge, with a corresponding reduction in Th1 and Th17 cytokines, as determined by Real Time RT-PCR. Furthermore, rBCG-LTAK63lo also displays protection against challenge with a highly virulent Beijing isolate. Our findings suggest that BCG with low-level expression of the LTAK63 adjuvant induces a stronger immune response in the lungs conferring higher levels of protection, and a novel mechanism subsequently triggers a regulatory immune response, which then limits the pathology. The rBCG-LTAK63lo strain can be the basis of an improved vaccine against tuberculosis. Medicine R Science Q Dunia Rodriguez verfasserin aut Carina C. Santos verfasserin aut Eduardo P. Amaral verfasserin aut Henrique K. Rofatto verfasserin aut Ana P. Junqueira-Kipnis verfasserin aut Eduardo D. C. Gonçalves verfasserin aut Maria R. D’Império-Lima verfasserin aut Mario H. Hirata verfasserin aut Celio L. Silva verfasserin aut Nathalie Winter verfasserin aut Brigitte Gicquel verfasserin aut Kingston H. G. Mills verfasserin aut Mariagrazia Pizza verfasserin aut Rino Rappuoli verfasserin aut Luciana C. C. Leite verfasserin aut In Scientific Reports Nature Portfolio, 2011 7(2017), 1, Seite 11 (DE-627)663366712 (DE-600)2615211-3 20452322 nnns volume:7 year:2017 number:1 pages:11 https://doi.org/10.1038/s41598-017-02003-9 kostenfrei https://doaj.org/article/df9d3306cb574c71b46f4ee32a1a4202 kostenfrei https://doi.org/10.1038/s41598-017-02003-9 kostenfrei https://doaj.org/toc/2045-2322 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_381 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4335 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 7 2017 1 11
allfieldsGer	10.1038/s41598-017-02003-9 doi (DE-627)DOAJ048424722 (DE-599)DOAJdf9d3306cb574c71b46f4ee32a1a4202 DE-627 ger DE-627 rakwb eng Ivan P. Nascimento verfasserin aut Recombinant BCG Expressing LTAK63 Adjuvant induces Superior Protection against Mycobacterium tuberculosis 2017 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract In order to develop an improved BCG vaccine against tuberculosis we have taken advantage of the adjuvant properties of a non-toxic derivative of Escherichia coli heat labile enterotoxin (LT), LTAK63. We have constructed rBCG strains expressing LTAK63 at different expression levels. Mice immunized with BCG expressing low levels of LTAK63 (rBCG-LTAK63lo) showed higher Th1 cytokines and IL-17 in the lungs, and when challenged intratracheally with Mycobacterium tuberculosis displayed a 2.0–3.0 log reduction in CFU as compared to wild type BCG. Histopathological analysis of lung tissues from protected mice revealed a reduced inflammatory response. Immunization with rBCG-LTAK63lo also protected against a 100-fold higher challenge dose. Mice immunized with rBCG-LTAK63lo produced an increase in TGF-β as compared with BCG after challenge, with a corresponding reduction in Th1 and Th17 cytokines, as determined by Real Time RT-PCR. Furthermore, rBCG-LTAK63lo also displays protection against challenge with a highly virulent Beijing isolate. Our findings suggest that BCG with low-level expression of the LTAK63 adjuvant induces a stronger immune response in the lungs conferring higher levels of protection, and a novel mechanism subsequently triggers a regulatory immune response, which then limits the pathology. The rBCG-LTAK63lo strain can be the basis of an improved vaccine against tuberculosis. Medicine R Science Q Dunia Rodriguez verfasserin aut Carina C. Santos verfasserin aut Eduardo P. Amaral verfasserin aut Henrique K. Rofatto verfasserin aut Ana P. Junqueira-Kipnis verfasserin aut Eduardo D. C. Gonçalves verfasserin aut Maria R. D’Império-Lima verfasserin aut Mario H. Hirata verfasserin aut Celio L. Silva verfasserin aut Nathalie Winter verfasserin aut Brigitte Gicquel verfasserin aut Kingston H. G. Mills verfasserin aut Mariagrazia Pizza verfasserin aut Rino Rappuoli verfasserin aut Luciana C. C. Leite verfasserin aut In Scientific Reports Nature Portfolio, 2011 7(2017), 1, Seite 11 (DE-627)663366712 (DE-600)2615211-3 20452322 nnns volume:7 year:2017 number:1 pages:11 https://doi.org/10.1038/s41598-017-02003-9 kostenfrei https://doaj.org/article/df9d3306cb574c71b46f4ee32a1a4202 kostenfrei https://doi.org/10.1038/s41598-017-02003-9 kostenfrei https://doaj.org/toc/2045-2322 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_381 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4335 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 7 2017 1 11
allfieldsSound	10.1038/s41598-017-02003-9 doi (DE-627)DOAJ048424722 (DE-599)DOAJdf9d3306cb574c71b46f4ee32a1a4202 DE-627 ger DE-627 rakwb eng Ivan P. Nascimento verfasserin aut Recombinant BCG Expressing LTAK63 Adjuvant induces Superior Protection against Mycobacterium tuberculosis 2017 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract In order to develop an improved BCG vaccine against tuberculosis we have taken advantage of the adjuvant properties of a non-toxic derivative of Escherichia coli heat labile enterotoxin (LT), LTAK63. We have constructed rBCG strains expressing LTAK63 at different expression levels. Mice immunized with BCG expressing low levels of LTAK63 (rBCG-LTAK63lo) showed higher Th1 cytokines and IL-17 in the lungs, and when challenged intratracheally with Mycobacterium tuberculosis displayed a 2.0–3.0 log reduction in CFU as compared to wild type BCG. Histopathological analysis of lung tissues from protected mice revealed a reduced inflammatory response. Immunization with rBCG-LTAK63lo also protected against a 100-fold higher challenge dose. Mice immunized with rBCG-LTAK63lo produced an increase in TGF-β as compared with BCG after challenge, with a corresponding reduction in Th1 and Th17 cytokines, as determined by Real Time RT-PCR. Furthermore, rBCG-LTAK63lo also displays protection against challenge with a highly virulent Beijing isolate. Our findings suggest that BCG with low-level expression of the LTAK63 adjuvant induces a stronger immune response in the lungs conferring higher levels of protection, and a novel mechanism subsequently triggers a regulatory immune response, which then limits the pathology. The rBCG-LTAK63lo strain can be the basis of an improved vaccine against tuberculosis. Medicine R Science Q Dunia Rodriguez verfasserin aut Carina C. Santos verfasserin aut Eduardo P. Amaral verfasserin aut Henrique K. Rofatto verfasserin aut Ana P. Junqueira-Kipnis verfasserin aut Eduardo D. C. Gonçalves verfasserin aut Maria R. D’Império-Lima verfasserin aut Mario H. Hirata verfasserin aut Celio L. Silva verfasserin aut Nathalie Winter verfasserin aut Brigitte Gicquel verfasserin aut Kingston H. G. Mills verfasserin aut Mariagrazia Pizza verfasserin aut Rino Rappuoli verfasserin aut Luciana C. C. Leite verfasserin aut In Scientific Reports Nature Portfolio, 2011 7(2017), 1, Seite 11 (DE-627)663366712 (DE-600)2615211-3 20452322 nnns volume:7 year:2017 number:1 pages:11 https://doi.org/10.1038/s41598-017-02003-9 kostenfrei https://doaj.org/article/df9d3306cb574c71b46f4ee32a1a4202 kostenfrei https://doi.org/10.1038/s41598-017-02003-9 kostenfrei https://doaj.org/toc/2045-2322 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_381 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4335 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 7 2017 1 11
language	English
source	In Scientific Reports 7(2017), 1, Seite 11 volume:7 year:2017 number:1 pages:11
sourceStr	In Scientific Reports 7(2017), 1, Seite 11 volume:7 year:2017 number:1 pages:11
format_phy_str_mv	Article
institution	findex.gbv.de
topic_facet	Medicine R Science Q
isfreeaccess_bool	true
container_title	Scientific Reports
authorswithroles_txt_mv	Ivan P. Nascimento @@aut@@ Dunia Rodriguez @@aut@@ Carina C. Santos @@aut@@ Eduardo P. Amaral @@aut@@ Henrique K. Rofatto @@aut@@ Ana P. Junqueira-Kipnis @@aut@@ Eduardo D. C. Gonçalves @@aut@@ Maria R. D’Império-Lima @@aut@@ Mario H. Hirata @@aut@@ Celio L. Silva @@aut@@ Nathalie Winter @@aut@@ Brigitte Gicquel @@aut@@ Kingston H. G. Mills @@aut@@ Mariagrazia Pizza @@aut@@ Rino Rappuoli @@aut@@ Luciana C. C. Leite @@aut@@
publishDateDaySort_date	2017-01-01T00:00:00Z
hierarchy_top_id	663366712
id	DOAJ048424722
language_de	englisch
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author	Ivan P. Nascimento
spellingShingle	Ivan P. Nascimento misc Medicine misc R misc Science misc Q Recombinant BCG Expressing LTAK63 Adjuvant induces Superior Protection against Mycobacterium tuberculosis
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topic_title	Recombinant BCG Expressing LTAK63 Adjuvant induces Superior Protection against Mycobacterium tuberculosis
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title	Recombinant BCG Expressing LTAK63 Adjuvant induces Superior Protection against Mycobacterium tuberculosis
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title_full	Recombinant BCG Expressing LTAK63 Adjuvant induces Superior Protection against Mycobacterium tuberculosis
author_sort	Ivan P. Nascimento
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author_browse	Ivan P. Nascimento Dunia Rodriguez Carina C. Santos Eduardo P. Amaral Henrique K. Rofatto Ana P. Junqueira-Kipnis Eduardo D. C. Gonçalves Maria R. D’Império-Lima Mario H. Hirata Celio L. Silva Nathalie Winter Brigitte Gicquel Kingston H. G. Mills Mariagrazia Pizza Rino Rappuoli Luciana C. C. Leite
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author-letter	Ivan P. Nascimento
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title_sort	recombinant bcg expressing ltak63 adjuvant induces superior protection against mycobacterium tuberculosis
title_auth	Recombinant BCG Expressing LTAK63 Adjuvant induces Superior Protection against Mycobacterium tuberculosis
abstract	Abstract In order to develop an improved BCG vaccine against tuberculosis we have taken advantage of the adjuvant properties of a non-toxic derivative of Escherichia coli heat labile enterotoxin (LT), LTAK63. We have constructed rBCG strains expressing LTAK63 at different expression levels. Mice immunized with BCG expressing low levels of LTAK63 (rBCG-LTAK63lo) showed higher Th1 cytokines and IL-17 in the lungs, and when challenged intratracheally with Mycobacterium tuberculosis displayed a 2.0–3.0 log reduction in CFU as compared to wild type BCG. Histopathological analysis of lung tissues from protected mice revealed a reduced inflammatory response. Immunization with rBCG-LTAK63lo also protected against a 100-fold higher challenge dose. Mice immunized with rBCG-LTAK63lo produced an increase in TGF-β as compared with BCG after challenge, with a corresponding reduction in Th1 and Th17 cytokines, as determined by Real Time RT-PCR. Furthermore, rBCG-LTAK63lo also displays protection against challenge with a highly virulent Beijing isolate. Our findings suggest that BCG with low-level expression of the LTAK63 adjuvant induces a stronger immune response in the lungs conferring higher levels of protection, and a novel mechanism subsequently triggers a regulatory immune response, which then limits the pathology. The rBCG-LTAK63lo strain can be the basis of an improved vaccine against tuberculosis.
abstractGer	Abstract In order to develop an improved BCG vaccine against tuberculosis we have taken advantage of the adjuvant properties of a non-toxic derivative of Escherichia coli heat labile enterotoxin (LT), LTAK63. We have constructed rBCG strains expressing LTAK63 at different expression levels. Mice immunized with BCG expressing low levels of LTAK63 (rBCG-LTAK63lo) showed higher Th1 cytokines and IL-17 in the lungs, and when challenged intratracheally with Mycobacterium tuberculosis displayed a 2.0–3.0 log reduction in CFU as compared to wild type BCG. Histopathological analysis of lung tissues from protected mice revealed a reduced inflammatory response. Immunization with rBCG-LTAK63lo also protected against a 100-fold higher challenge dose. Mice immunized with rBCG-LTAK63lo produced an increase in TGF-β as compared with BCG after challenge, with a corresponding reduction in Th1 and Th17 cytokines, as determined by Real Time RT-PCR. Furthermore, rBCG-LTAK63lo also displays protection against challenge with a highly virulent Beijing isolate. Our findings suggest that BCG with low-level expression of the LTAK63 adjuvant induces a stronger immune response in the lungs conferring higher levels of protection, and a novel mechanism subsequently triggers a regulatory immune response, which then limits the pathology. The rBCG-LTAK63lo strain can be the basis of an improved vaccine against tuberculosis.
abstract_unstemmed	Abstract In order to develop an improved BCG vaccine against tuberculosis we have taken advantage of the adjuvant properties of a non-toxic derivative of Escherichia coli heat labile enterotoxin (LT), LTAK63. We have constructed rBCG strains expressing LTAK63 at different expression levels. Mice immunized with BCG expressing low levels of LTAK63 (rBCG-LTAK63lo) showed higher Th1 cytokines and IL-17 in the lungs, and when challenged intratracheally with Mycobacterium tuberculosis displayed a 2.0–3.0 log reduction in CFU as compared to wild type BCG. Histopathological analysis of lung tissues from protected mice revealed a reduced inflammatory response. Immunization with rBCG-LTAK63lo also protected against a 100-fold higher challenge dose. Mice immunized with rBCG-LTAK63lo produced an increase in TGF-β as compared with BCG after challenge, with a corresponding reduction in Th1 and Th17 cytokines, as determined by Real Time RT-PCR. Furthermore, rBCG-LTAK63lo also displays protection against challenge with a highly virulent Beijing isolate. Our findings suggest that BCG with low-level expression of the LTAK63 adjuvant induces a stronger immune response in the lungs conferring higher levels of protection, and a novel mechanism subsequently triggers a regulatory immune response, which then limits the pathology. The rBCG-LTAK63lo strain can be the basis of an improved vaccine against tuberculosis.
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title_short	Recombinant BCG Expressing LTAK63 Adjuvant induces Superior Protection against Mycobacterium tuberculosis
url	https://doi.org/10.1038/s41598-017-02003-9 https://doaj.org/article/df9d3306cb574c71b46f4ee32a1a4202 https://doaj.org/toc/2045-2322
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Recombinant BCG Expressing LTAK63 Adjuvant induces Superior Protection against Mycobacterium tuberculosis

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