Exchanging ESAT6 with TB10.4 in an Ag85B fusion molecule-based tuberculosis subunit vaccine: efficient protection and ESAT6-based sensitive monitoring of vaccine efficacy.
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.
Dietrich
Jes
J
Department of Infectious Disease Immunology, Statens Serum Institute, Copenhagen, Denmark. jdi@ssi.dk
Aagaard
Claus
C
Leah
Robert
R
Olsen
Anja W
AW
Stryhn
Anette
A
Doherty
T Mark
TM
Andersen
Peter
P
D000217:Acyltransferases / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D000595:Amino Acid Sequence; D000818:Animals; D000942:Antigens, Bacterial / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D001426:Bacterial Proteins / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D001483:Base Sequence; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D015169:Colony Count, Microbial; D018984:Epitopes, T-Lymphocyte / Q000276:immunology / Q000378:metabolism; D005260:Female; D007371:Interferon-gamma / Q000096:biosynthesis; D008168:Lung / Q000276:immunology / Q000382:microbiology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D032581:Tuberculosis Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D014397:Tuberculosis, Pulmonary / Q000175:diagnosis / Q000276:immunology / Q000517:prevention & control; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D022223:Vaccines, Subunit / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology
D000942:Antigens, Bacterial; D001426:Bacterial Proteins; C093276:ESAT-6 protein, Mycobacterium tuberculosis; D018984:Epitopes, T-Lymphocyte; D011993:Recombinant Fusion Proteins; C501710:TB10.4 antigen, Mycobacterium tuberculosis; D032581:Tuberculosis Vaccines; D019444:Vaccines, DNA; D022223:Vaccines, Subunit; D007371:Interferon-gamma; D000217:Acyltransferases; C121433:antigen 85B, Mycobacterium tuberculosis