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

Nacho Aguilo (), Jesus Gonzalo-Asensio, Samuel Alvarez-Arguedas, Dessislava Marinova, Ana Belen Gomez, Santiago Uranga, Ralf Spallek, Mahavir Singh, Regine Audran, François Spertini and Carlos Martin ()
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Nacho Aguilo: Grupo de Genética de Micobacterias, Dpto. Microbiología, Medicina Preventiva y Salud Pública, Universidad de Zaragoza
Jesus Gonzalo-Asensio: Grupo de Genética de Micobacterias, Dpto. Microbiología, Medicina Preventiva y Salud Pública, Universidad de Zaragoza
Samuel Alvarez-Arguedas: Grupo de Genética de Micobacterias, Dpto. Microbiología, Medicina Preventiva y Salud Pública, Universidad de Zaragoza
Dessislava Marinova: Grupo de Genética de Micobacterias, Dpto. Microbiología, Medicina Preventiva y Salud Pública, Universidad de Zaragoza
Ana Belen Gomez: Grupo de Genética de Micobacterias, Dpto. Microbiología, Medicina Preventiva y Salud Pública, Universidad de Zaragoza
Santiago Uranga: Grupo de Genética de Micobacterias, Dpto. Microbiología, Medicina Preventiva y Salud Pública, Universidad de Zaragoza
Ralf Spallek: LIONEX GmbH
Mahavir Singh: LIONEX GmbH
Regine Audran: Centre Hospitalier Universitaire Vaudois (CHUV)
François Spertini: Centre Hospitalier Universitaire Vaudois (CHUV)
Carlos Martin: Grupo de Genética de Micobacterias, Dpto. Microbiología, Medicina Preventiva y Salud Pública, Universidad de Zaragoza

Nature Communications, 2017, vol. 8, issue 1, 1-11

Abstract: Abstract 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.

Date: 2017
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DOI: 10.1038/ncomms16085

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