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

被引：112
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
来源：
VACCINE | 2006年 / 24卷 / 26期
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
相关论文
共 35 条
[1]   T-CELL PROLIFERATIVE RESPONSE TO ANTIGENS SECRETED BY MYCOBACTERIUM-TUBERCULOSIS [J].
ANDERSEN, P ;
ASKGAARD, D ;
LJUNGQVIST, L ;
BENTZON, MW ;
HERON, I .
INFECTION AND IMMUNITY, 1991, 59 (04) :1558-1563
[2]   EFFECTIVE VACCINATION OF MICE AGAINST MYCOBACTERIUM-TUBERCULOSIS INFECTION WITH A SOLUBLE MIXTURE OF SECRETED MYCOBACTERIAL PROTEINS [J].
ANDERSEN, P .
INFECTION AND IMMUNITY, 1994, 62 (06) :2536-2544
[3]   The protective effect of the Mycobacterium bovis BCG vaccine is increased by coadministration with the Mycobacterium tuberculosis 72-kilodalton fusion polyprotein Mtb72F in M-tuberculosis-infected guinea pigs [J].
Brandt, L ;
Skeiky, YAW ;
Alderson, MR ;
Lobet, Y ;
Dalemans, W ;
Turner, OC ;
Basaraba, RJ ;
Izzo, AA ;
Lasco, TM ;
Chapman, PL ;
Reed, SG ;
Orme, IM .
INFECTION AND IMMUNITY, 2004, 72 (11) :6622-6632
[4]   Failure of the Mycobacterium bovis BCG vaccine:: Some species of environmental mycobacteria block multiplication of BCG and induction of protective immunity to tuberculosis [J].
Brandt, L ;
Cunha, JF ;
Olsen, AW ;
Chilima, B ;
Hirsch, P ;
Appelberg, R ;
Andersen, P .
INFECTION AND IMMUNITY, 2002, 70 (02) :672-678
[5]   FREUND COMPLETE ADJUVANT - AN EFFECTIVE BUT DISAGREEABLE FORMULA [J].
CLAASSEN, E ;
DELEEUW, W ;
DEGREEVE, P ;
HENDRIKSEN, C ;
BOERSMA, W .
RESEARCH IN IMMUNOLOGY, 1992, 143 (05) :478-483
[6]   Safety and immunogenicity of CPG 7909 injection as an adjuvant to Fluarix influenza vaccine [J].
Cooper, CL ;
Davis, HL ;
Morris, ML ;
Efler, SM ;
Krieg, AM ;
Li, Y ;
Laframboise, C ;
Al Adhami, MJ ;
Khaliq, Y ;
Seguin, I ;
Cameron, DW .
VACCINE, 2004, 22 (23-24) :3136-3143
[7]   Lipoplex-mediated delivery of nucleic acids: factors affecting in vivo transfection [J].
Dass, CR .
JOURNAL OF MOLECULAR MEDICINE-JMM, 2004, 82 (09) :579-591
[8]   B-cell epitopes and quantification of the ESAT-6 protein of Mycobacterium tuberculosis [J].
Harboe, M ;
Malin, AS ;
Dockrell, HS ;
Wiker, HG ;
Ulvund, G ;
Holm, A ;
Jorgensen, MC ;
Andersen, P .
INFECTION AND IMMUNITY, 1998, 66 (02) :717-723
[9]   Recombinant bacillus Calmette-Guerin (BCG) vaccines expressing the Mycobacterium tuberculosis 30-kDa major secretory protein induce greater protective immunity against tuberculosis than conventional BCG vaccines in a highly susceptible animal model [J].
Horwitz, MA ;
Harth, G ;
Dillon, BJ ;
Maslesa-Galic, S .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2000, 97 (25) :13853-13858
[10]   Enhancing the protective efficacy of Mycobacterium bovis BCG vaccination against tuberculosis by boosting with the Mycobacterium tuberculosis major secretory protein [J].
Horwitz, MA ;
Harth, G ;
Dillon, BJ ;
Maslesa-Galic, S .
INFECTION AND IMMUNITY, 2005, 73 (08) :4676-4683
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