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

Aguilo, Nacho (Universidad de Zaragoza) ; Gonzalo-Asensio, Jesús (Universidad de Zaragoza) ; Alvarez-Arguedas, Samuel (Universidad de Zaragoza) ; Marinova, Dessislava (Universidad de Zaragoza) ; Gomez, Ana Belen (Universidad de Zaragoza) ; Uranga, Santiago (Universidad de Zaragoza) ; Spallek, Ralf ; Singh, Mahavir ; Audran, Regine ; Spertini, François ; Martin, Carlos (Universidad de Zaragoza)

Resumen: 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.

Idioma: Inglés

DOI: 10.1038/ncomms16085

Año: 2017

Publicado en: Nature Communications 8 (2017), 16085 [11 pp.]
ISSN: 2041-1723

Factor impacto JCR: 12.353 (2017)

Categ. JCR: MULTIDISCIPLINARY SCIENCES rank: 3 / 64 = 0.047 (2017) - Q1 - T1

Factor impacto SCIMAGO: 6.582 - Biochemistry, Genetics and Molecular Biology (miscellaneous) (Q1) - Physics and Astronomy (miscellaneous) (Q1) - Chemistry (miscellaneous) (Q1)

Financiación: info:eu-repo/grantAgreement/EC/H2020/643381/EU/TBVAC2020; Advancing novel and promising TB vaccine candidates from discovery to preclinical and early clinical development/TBVAC2020
Financiación: info:eu-repo/grantAgreement/ES/MINECO/BIO2014-5258P

Tipo y forma: Article (Published version)

Área (Departamento): Área Microbiología (Dpto. Microb.Med.Pr.,Sal.Públ.)
Área (Departamento): Proy. investigación HQA (Dpto. Microb.Med.Pr.,Sal.Públ.)