Exchanging ESAT6 with TB10.4 in an Ag85B fusion molecule-based tuberculosis subunit vaccine: Efficient protection and ESAT6-based sensitive monitoring of vaccine efficacy

被引:201
作者
Dietrich, J [1 ]
Aagaard, C [1 ]
Leah, R [1 ]
Olsen, AW [1 ]
Stryhn, A [1 ]
Doherty, TM [1 ]
Andersen, P [1 ]
机构
[1] Statens Serum Inst, Dept Infect Dis Immunol, DK-2300 Copenhagen, Denmark
关键词
D O I
10.4049/jimmunol.174.10.6332
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Previously we have shown that Ag85B-ESAT-6 is a highly efficient vaccine against tuberculosis. However, because the ESAT-6 Ag is also an extremely valuable diagnostic reagent, finding a vaccine as effective as Ag85B-ESAT-6 that does not contain ESAT-6 is a high priority. Recently, we identified a novel protein expressed by Mycobacterium tuberculosis designated TB10.4. In most infected humans, TB10.4 is strongly recognized, raising interest in TB10.4 as a potential vaccine candidate and substitute for ESAT-6. We have now examined the vaccine potential of this protein and found that vaccination with TB10.4 induced a significant protection against tuberculosis. Fusing Ag85B to TB10.4 produced an even more effective vaccine, which induced protection against tuberculosis comparable to bacillus Calmette-Guerin vaccination and superior to the individual Ag components. Thus, Ag85B-TB10 represents a new promising vaccine candidate against tuberculosis. Furthermore, having now exchanged ESAT-6 for TB10.4, we show that ESAT-6, apart from being an excellent diagnostic reagent, can also be used as a reagent for monitoring vaccine efficacy. This may open a new way for monitoring vaccine efficacy in clinical trials.
引用
收藏
页码:6332 / 6339
页数:8
相关论文
共 39 条
[2]  
Brandt L, 1996, J IMMUNOL, V157, P3527
[3]   ESAT-6 subunit vaccination against Mycobacterium tuberculosis [J].
Brandt, L ;
Elhay, M ;
Rosenkrands, I ;
Lindblad, EB ;
Andersen, P .
INFECTION AND IMMUNITY, 2000, 68 (02) :791-795
[4]   Preventing tuberculosis with bacillus Calmette-Guerin vaccine: A meta-analysis of the literature [J].
Brewer, TF .
CLINICAL INFECTIOUS DISEASES, 2000, 31 :S64-S67
[5]   BACILLE CALMETTE-GUERIN VACCINATION FOR THE PREVENTION OF TUBERCULOSIS IN HEALTH-CARE WORKERS [J].
BREWER, TF ;
COLDITZ, GA .
CLINICAL INFECTIOUS DISEASES, 1995, 20 (01) :136-142
[6]   Specific T-cell epitopes for immunoassay-based diagnosis of Mycobacterium tuberculosis infection [J].
Brock, I ;
Weldingh, K ;
Leyten, EMS ;
Arend, SM ;
Ravn, P ;
Andersen, P .
JOURNAL OF CLINICAL MICROBIOLOGY, 2004, 42 (06) :2379-2387
[7]   EFFECT OF MONOPHOSPHORYL LIPID-A ON THE INVITRO FUNCTION OF PERITONEAL LEUKOCYTES FROM UREMIC PATIENTS ON CONTINUOUS AMBULATORY PERITONEAL-DIALYSIS [J].
CAROZZI, S ;
SALIT, M ;
CANTALUPPI, A ;
NASINI, MG ;
BAROCCI, S ;
CANTARELLA, S ;
LAMPERI, S .
JOURNAL OF CLINICAL MICROBIOLOGY, 1989, 27 (08) :1748-1753
[8]   EFFICACY OF BCG VACCINE IN THE PREVENTION OF TUBERCULOSIS - METAANALYSIS OF THE PUBLISHED LITERATURE [J].
COLDITZ, GA ;
BREWER, TF ;
BERKEY, CS ;
WILSON, ME ;
BURDICK, E ;
FINEBERG, HV ;
MOSTELLER, F .
JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, 1994, 271 (09) :698-702
[9]   Deciphering the biology of Mycobacterium tuberculosis from the complete genome sequence [J].
Cole, ST ;
Brosch, R ;
Parkhill, J ;
Garnier, T ;
Churcher, C ;
Harris, D ;
Gordon, SV ;
Eiglmeier, K ;
Gas, S ;
Barry, CE ;
Tekaia, F ;
Badcock, K ;
Basham, D ;
Brown, D ;
Chillingworth, T ;
Connor, R ;
Davies, R ;
Devlin, K ;
Feltwell, T ;
Gentles, S ;
Hamlin, N ;
Holroyd, S ;
Hornby, T ;
Jagels, K ;
Krogh, A ;
McLean, J ;
Moule, S ;
Murphy, L ;
Oliver, K ;
Osborne, J ;
Quail, MA ;
Rajandream, MA ;
Rogers, J ;
Rutter, S ;
Seeger, K ;
Skelton, J ;
Squares, R ;
Squares, S ;
Sulston, JE ;
Taylor, K ;
Whitehead, S ;
Barrell, BG .
NATURE, 1998, 393 (6685) :537-+
[10]   Comparative analysis of different vaccine constructs expressing defined antigens from Mycobacterium tuberculosis [J].
Doherty, TM ;
Olsen, AW ;
Weischenfeldt, J ;
Huygen, K ;
D'Souza, S ;
Kondratieva, TK ;
Yeremeev, VV ;
Apt, AS ;
Raupach, BR ;
Grode, L ;
Kaufmann, S ;
Andersen, P .
JOURNAL OF INFECTIOUS DISEASES, 2004, 190 (12) :2146-2153