Induction of protective immunity against Mycobacterium tuberculosis by delivery of ESX antigens into airway dendritic cells

0422897 - MBÚ 2014 RIV US eng J - Journal Article
Dong, H. - Staněk, Ondřej - Rudilla, F. S. - Langer, U. - Morillon, E. - Ung, C. - Šebo, Peter - Leclerc, C. - Majlessi, L.
Induction of protective immunity against Mycobacterium tuberculosis by delivery of ESX antigens into airway dendritic cells.
Mucosal Immunology. Roč. 6, č. 3 (2013), s. 522-534. ISSN 1933-0219. E-ISSN 1935-3456
R&D Projects: GA AV ČR KAN200520702
Institutional support: RVO:61388971
Keywords : T-CELLS * IN-VIVO * RECEPTOR DEC-205
Subject RIV: EE - Microbiology, Virology
Impact factor: 7.537, year: 2013

As the Bacillus Calmette-Guerin (BCG) vaccine does not confer long-lasting protection against lung Mycobacterium tuberculosis infection, the development of more efficient vaccines is greatly needed. Here, we used mycobacterial low-molecular weight proteins of the 6-kDa Early Secreted Antigenic Target (ESAT-6) protein family (ESX) antigens for the evaluation of a novel vaccine delivery strategy that enables versatile in vivo targeting of antigens into specialized dendritic cell (DC) subsets. ESX antigens were genetically fused to the tetramerizing core of streptavidin (SA) to form high-affinity complexes with biotin (biot)-conjugated antibodies recognizing DC surface receptors. When directed through the CD11b or CD11c beta(2)-integrins or diverse C-type lectins, the ESX-SA:biot-antibody complexes were efficiently captured and presented on major histocompatibility complex molecules of DCs to specific T-cell receptors. Robust ESX-specific T-cell responses were induced by immunization with as little as several picomoles of ESX-SA targeted to DC subsets. Moreover, directing of TB10.4-SA to airway CD205(+) cells enabled the induction of mucosal T-cell responses and provided significant protection against virulent M. tuberculosis
Permanent Link: http://hdl.handle.net/11104/0229027