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

Aguilo, N.; Gonzalo-Asensio, J.; Alvarez-Arguedas, S.; Marinova, D.; Gomez, A.B.; Uranga, S.; Spallek, R.; Singh, M.; Audran, R.; Spertini, F.; Martin, C.

doi:10.1038/ncomms16085

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

Details

Download: 28706226_BIB_6B52857B61DD.pdf (1013.74 [Ko])
State: Public
Version: Final published version
License: CC BY 4.0

Serval ID

serval:BIB_6B52857B61DD

Type

Article: article from journal or magazin.

Collection

Publications

Institution

UNIL/CHUV

Title

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

Journal

Nature communications

Author(s)

Aguilo N., Gonzalo-Asensio J., Alvarez-Arguedas S., Marinova D., Gomez A.B., Uranga S., Spallek R., Singh M., Audran R., Spertini F., Martin C.

ISSN

2041-1723 (Electronic)

ISSN-L

2041-1723

Publication state

Published

Issued date

14/07/2017

Peer-reviewed

Oui

Volume

Pages

16085

Language

english

Notes

Publication types: Comparative Study ; Evaluation Studies ; Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: epublish

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.

Keywords

Animals, Antigens, Bacterial/genetics, Antigens, Bacterial/immunology, Bacterial Proteins/genetics, Bacterial Proteins/immunology, Female, Gene Expression, Host-Pathogen Interactions/genetics, Mice, Inbred Strains, Mycobacterium tuberculosis, Tuberculosis Vaccines/immunology

URN

urn:nbn:ch:serval-BIB_6B52857B61DD4

OAI-PMH

oai:serval.unil.ch:BIB_6B52857B61DD

DOI

10.1038/ncomms16085

Pubmed

28706226

Web of science

000405465600002

Open Access

Yes