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Induction of protective immunity against Mycobacterium tuberculosis by delivery of ESX antigens into airway dendritic cells.
MedLine Citation:
PMID:  23032790     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
As the Bacillus Calmette-Guérin (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 β(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.Mucosal Immunology advance online publication 3 October 2012; doi:10.1038/mi.2012.92.
Authors:
H Dong; O Stanek; F Rudilla Salvador; U Länger; E Morillon; C Ung; P Sebo; C Leclerc; L Majlessi
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-10-03
Journal Detail:
Title:  Mucosal immunology     Volume:  -     ISSN:  1935-3456     ISO Abbreviation:  Mucosal Immunol     Publication Date:  2012 Oct 
Date Detail:
Created Date:  2012-10-3     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101299742     Medline TA:  Mucosal Immunol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
1] Institut Pasteur, Unité de Régulation Immunitaire et Vaccinologie, Paris, France [2] INSERM U1041, Paris, France [3] Jiangsu Key Laboratory of Zoonosis, Yangzhou University, Yangzhou, Jiangsu, China.
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