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

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  • Nacho Aguilo

    (Grupo de Genética de Micobacterias, Dpto. Microbiología, Medicina Preventiva y Salud Pública, Universidad de Zaragoza
    CIBER Enfermedades Respiratorias, Instituto de Salud Carlos III)

  • Jesus Gonzalo-Asensio

    (Grupo de Genética de Micobacterias, Dpto. Microbiología, Medicina Preventiva y Salud Pública, Universidad de Zaragoza
    CIBER Enfermedades Respiratorias, Instituto de Salud Carlos III)

  • Samuel Alvarez-Arguedas

    (Grupo de Genética de Micobacterias, Dpto. Microbiología, Medicina Preventiva y Salud Pública, Universidad de Zaragoza
    CIBER Enfermedades Respiratorias, Instituto de Salud Carlos III)

  • Dessislava Marinova

    (Grupo de Genética de Micobacterias, Dpto. Microbiología, Medicina Preventiva y Salud Pública, Universidad de Zaragoza
    CIBER Enfermedades Respiratorias, Instituto de Salud Carlos III)

  • Ana Belen Gomez

    (Grupo de Genética de Micobacterias, Dpto. Microbiología, Medicina Preventiva y Salud Pública, Universidad de Zaragoza
    CIBER Enfermedades Respiratorias, Instituto de Salud Carlos III)

  • Santiago Uranga

    (Grupo de Genética de Micobacterias, Dpto. Microbiología, Medicina Preventiva y Salud Pública, Universidad de Zaragoza
    CIBER Enfermedades Respiratorias, Instituto de Salud Carlos III)

  • 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
    CIBER Enfermedades Respiratorias, Instituto de Salud Carlos III
    Servicio de Microbiología, Hospital Universitario Miguel Servet, ISS Aragón)

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.

Suggested Citation

  • Nacho Aguilo & Jesus Gonzalo-Asensio & Samuel Alvarez-Arguedas & Dessislava Marinova & Ana Belen Gomez & Santiago Uranga & Ralf Spallek & Mahavir Singh & Regine Audran & François Spertini & Carlos Mar, 2017. "Reactogenicity to major tuberculosis antigens absent in BCG is linked to improved protection against Mycobacterium tuberculosis," Nature Communications, Nature, vol. 8(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_ncomms16085
    DOI: 10.1038/ncomms16085
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    Cited by:

    1. Elena Campos-Pardos & Santiago Uranga & Ana Picó & Ana Belén Gómez & Jesús Gonzalo-Asensio, 2024. "Dependency on host vitamin B12 has shaped Mycobacterium tuberculosis Complex evolution," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    2. Joshua S. Woodworth & Helena Strand Clemmensen & Hannah Battey & Karin Dijkman & Thomas Lindenstrøm & Raquel Salvador Laureano & Randy Taplitz & Jeffrey Morgan & Claus Aagaard & Ida Rosenkrands & Ceci, 2021. "A Mycobacterium tuberculosis-specific subunit vaccine that provides synergistic immunity upon co-administration with Bacillus Calmette-Guérin," Nature Communications, Nature, vol. 12(1), pages 1-13, December.

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