Exchanging ESAT6 with TB10.4 in an Ag85B Fusion Molecule-Based Tuberculosis Subunit Vaccine: Efficient Protection and ESAT6-Based Sensitive Monitoring of Vaccine Efficacy

• Published in: The Journal of immunology (1950) 2005-05, Vol.174 (10), p.6332-6339
• Main Authors: Dietrich, Jes, Aagaard, Claus, Leah, Robert, Olsen, Anja W, Stryhn, Anette, Doherty, T. Mark, Andersen, Peter
• Format: Article
• Language: English
• Subjects: Acyltransferases - administration & dosage; Acyltransferases - genetics; Acyltransferases - immunology; Amino Acid Sequence; Animals; Antigens, Bacterial - administration & dosage; Antigens, Bacterial - genetics; Antigens, Bacterial - immunology; Bacterial Proteins - administration & dosage; Bacterial Proteins - genetics; Bacterial Proteins - immunology; Base Sequence; CD4-Positive T-Lymphocytes - immunology; CD4-Positive T-Lymphocytes - metabolism; CD4-Positive T-Lymphocytes - microbiology; Colony Count, Microbial; Epitopes, T-Lymphocyte - immunology; Epitopes, T-Lymphocyte - metabolism; Female; Interferon-gamma - biosynthesis; Lung - immunology; Lung - microbiology; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Molecular Sequence Data; Mycobacterium tuberculosis; Recombinant Fusion Proteins - administration & dosage; Recombinant Fusion Proteins - genetics; Recombinant Fusion Proteins - immunology; Tuberculosis Vaccines - administration & dosage; Tuberculosis Vaccines - genetics; Tuberculosis Vaccines - immunology; Tuberculosis, Pulmonary - diagnosis; Tuberculosis, Pulmonary - immunology; Tuberculosis, Pulmonary - prevention & control; Vaccines, DNA - administration & dosage; Vaccines, DNA - genetics; Vaccines, DNA - immunology; Vaccines, Subunit - administration & dosage; Vaccines, Subunit - genetics; Vaccines, Subunit - immunology
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.174.10.6332

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.