Reactogenicity to major tuberculosis antigens absent in BCG is linked to improved protection against Mycobacterium tuberculosis

MTBVAC is a live-attenuated Mycobacterium tuberculosis vaccine, currently under clinical development, that contains the major antigens ESAT6 and CFP10. These antigens are absent from the current tuberculosis vaccine, BCG. Here we compare the protection induced by BCG and MTBVAC in several mouse stra...

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Autores principales: Aguilo, Nacho, Gonzalo-Asensio, Jesus, Alvarez-Arguedas, Samuel, Marinova, Dessislava, Gomez, Ana Belen, Uranga, Santiago, Spallek, Ralf, Singh, Mahavir, Audran, Regine, Spertini, François, Martin, Carlos
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2017
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Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5519979/
https://www.ncbi.nlm.nih.gov/pubmed/28706226
http://dx.doi.org/10.1038/ncomms16085
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author Aguilo, Nacho
Gonzalo-Asensio, Jesus
Alvarez-Arguedas, Samuel
Marinova, Dessislava
Gomez, Ana Belen
Uranga, Santiago
Spallek, Ralf
Singh, Mahavir
Audran, Regine
Spertini, François
Martin, Carlos
author_facet Aguilo, Nacho
Gonzalo-Asensio, Jesus
Alvarez-Arguedas, Samuel
Marinova, Dessislava
Gomez, Ana Belen
Uranga, Santiago
Spallek, Ralf
Singh, Mahavir
Audran, Regine
Spertini, François
Martin, Carlos
author_sort Aguilo, Nacho
collection PubMed
description MTBVAC is a live-attenuated Mycobacterium tuberculosis vaccine, currently under clinical development, that contains the major antigens ESAT6 and CFP10. These antigens are absent from the current tuberculosis vaccine, BCG. Here we compare the protection induced by BCG and MTBVAC in several mouse strains that naturally express different MHC haplotypes differentially recognizing ESAT6 and CFP10. MTBVAC induces improved protection in C3H mice, the only of the three tested strains reactive to both ESAT6 and CFP10. Deletion of both antigens in MTBVAC reduces its efficacy to BCG levels, supporting a link between greater efficacy and CFP10- and ESAT6-specific reactogenicity. In addition, MTBVAC (but not BCG) triggers a specific response in human vaccinees against ESAT6 and CFP10. Our results warrant further exploration of this response as potential biomarker of protection in MTBVAC clinical trials.
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spelling pubmed-55199792017-07-28 Reactogenicity to major tuberculosis antigens absent in BCG is linked to improved protection against Mycobacterium tuberculosis Aguilo, Nacho Gonzalo-Asensio, Jesus Alvarez-Arguedas, Samuel Marinova, Dessislava Gomez, Ana Belen Uranga, Santiago Spallek, Ralf Singh, Mahavir Audran, Regine Spertini, François Martin, Carlos Nat Commun Article MTBVAC is a live-attenuated Mycobacterium tuberculosis vaccine, currently under clinical development, that contains the major antigens ESAT6 and CFP10. These antigens are absent from the current tuberculosis vaccine, BCG. Here we compare the protection induced by BCG and MTBVAC in several mouse strains that naturally express different MHC haplotypes differentially recognizing ESAT6 and CFP10. MTBVAC induces improved protection in C3H mice, the only of the three tested strains reactive to both ESAT6 and CFP10. Deletion of both antigens in MTBVAC reduces its efficacy to BCG levels, supporting a link between greater efficacy and CFP10- and ESAT6-specific reactogenicity. In addition, MTBVAC (but not BCG) triggers a specific response in human vaccinees against ESAT6 and CFP10. Our results warrant further exploration of this response as potential biomarker of protection in MTBVAC clinical trials. Nature Publishing Group 2017-07-14 /pmc/articles/PMC5519979/ /pubmed/28706226 http://dx.doi.org/10.1038/ncomms16085 Text en Copyright © 2017, The Author(s) http://creativecommons.org/licenses/by/4.0/ Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Aguilo, Nacho
Gonzalo-Asensio, Jesus
Alvarez-Arguedas, Samuel
Marinova, Dessislava
Gomez, Ana Belen
Uranga, Santiago
Spallek, Ralf
Singh, Mahavir
Audran, Regine
Spertini, François
Martin, Carlos
Reactogenicity to major tuberculosis antigens absent in BCG is linked to improved protection against Mycobacterium tuberculosis
title Reactogenicity to major tuberculosis antigens absent in BCG is linked to improved protection against Mycobacterium tuberculosis
title_full Reactogenicity to major tuberculosis antigens absent in BCG is linked to improved protection against Mycobacterium tuberculosis
title_fullStr Reactogenicity to major tuberculosis antigens absent in BCG is linked to improved protection against Mycobacterium tuberculosis
title_full_unstemmed Reactogenicity to major tuberculosis antigens absent in BCG is linked to improved protection against Mycobacterium tuberculosis
title_short Reactogenicity to major tuberculosis antigens absent in BCG is linked to improved protection against Mycobacterium tuberculosis
title_sort reactogenicity to major tuberculosis antigens absent in bcg is linked to improved protection against mycobacterium tuberculosis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5519979/
https://www.ncbi.nlm.nih.gov/pubmed/28706226
http://dx.doi.org/10.1038/ncomms16085
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