Protective immunity to tuberculosis with Ag85B-ESAT-6 in a synthetic cationic adjuvant system IC31

被引:110
作者
Agger, Else Marie
Rosenkrands, Ida
Olsen, Anja Weinreich
Hatch, Graham
Williams, Ann
Kritsch, Constantia
Lingnau, Karen
von Gabain, Alexander
Andersen, Claire Swetman
Korsholm, Karen Smith
Andersen, Peter
机构
[1] Statens Serum Inst, Dept Infect Dis Immunol, Adjuvant Res, DK-2300 Copenhagen S, Denmark
[2] Hlth Protect Agcy, Ctr Emergency Preparedness & Response, Salisbury SP4 0JG, Wilts, England
[3] Intercell AG, A-1030 Vienna, Austria
关键词
tuberculosis; vaccine; adjuvant;
D O I
10.1016/j.vaccine.2006.03.072
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
In this study, we evaluated the potential of a novel synthetic adjuvant designated 101 for the ability to augment the immune response and protective efficacy of the well-known mycobacterial vaccine antigen, Ag85B-ESAT-6. The IC31 adjuvant, consisting of a vehicle based on the cationic peptide KLKL5KLK and the immunostimulatory oligodeoxynucleotide ODN1a signalling through the TLR9 receptor, was found to promote highly efficient Th1 responses. The combination of Ag85B-ESAT-6 and IC31 exhibited significant levels of protection in the mouse aerosol challenge model of tuberculosis and a detailed analysis of the immune response generated revealed the induction of CD4 T cells giving rise to high levels of IFN-gamma secretion. Furthermore, the combination of Ag85B-ESAT-6/IC31 was found to confer efficient protection in the guinea pig aerosol model of tuberculosis infection and is at present moving towards clinical testing. (c) 2006 Elsevier Ltd. All rights reserved.
引用
收藏
页码:5452 / 5460
页数:9
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