Vaccine potential of influenza vectors expressing Mycobacterium tuberculosis ESAT-6 protein

• Published in: Tuberculosis (Edinburgh, Scotland) Vol. 86; no. 3; pp. 236 - 246
• Main Authors: Stukova, M.A., Sereinig, S., Zabolotnyh, N.V., Ferko, B., Kittel, C., Romanova, J., Vinogradova, T.I., Katinger, H., Kiselev, O.I., Egorov, A.
• Format: Journal Article
• Language: English
• Published: Scotland Elsevier Ltd 01.05.2006
• Subjects: Administration, Intranasal; Animals; Antigens, Bacterial - genetics; Antigens, Bacterial - immunology; Antigens, Bacterial - therapeutic use; Antitubercular Agents - therapeutic use; Bacterial Proteins - genetics; Bacterial Proteins - immunology; Bacterial Proteins - therapeutic use; Combined Modality Therapy; ESAT-6; Genetic Vectors - administration & dosage; Immunity, Cellular; Immunization - methods; Influenza; Influenza A virus - genetics; Isoniazid - therapeutic use; Mice; Mice, Inbred C57BL; Mycobacterium tuberculosis; Mycobacterium tuberculosis - immunology; Th1 Cells - immunology; Therapy; Tuberculosis - immunology; Tuberculosis - prevention & control; Tuberculosis - therapy; Tuberculosis vaccine; Tuberculosis Vaccines - immunology; Tuberculosis Vaccines - therapeutic use; Therapy; Tuberculosis vaccine; ESAT-6; Influenza
• ISSN: 1472-9792; 1873-281X
• DOI: 10.1016/j.tube.2006.01.010

We generated several attenuated recombinant influenza A vectors expressing the Mycobacterium tuberculosis early secretory antigenic target (ESAT-6) protein. The ESAT-6 protein was recently identified as one of the most promising protective antigens for cell-mediated immunity. The obtained vectors appeared to be capable of inducing ESAT-6 specific Th1 immune response in mice after intranasal immunization. We found that double immunization with two influenza vectors of different subtypes provided a significant level of protection in mice, when applied as prophylactic vaccine, as well as substantial therapeutic effect in mice with pre-established tuberculosis infection. Moreover, we found a strong synergistic effect when vaccination with Flu/ESAT-6 vectors was combined with isoniazid treatment, resulting in a dramatic reduction of bacterial load in the lungs of infected mice.