Mucosal Influenza Vector Vaccine Carrying TB10.4 and HspX Antigens Provides Protection against Mycobacterium tuberculosis in Mice and Guinea Pigs
| Autor: | Andrey V. Vasin, Yana A. Zabrodskaya, Mariia Sergeeva, Tatiana Vinogradova, Marina Stukova, A. A. Pulkina, Natalia Zabolotnyh, Artem Fadeev, Anna Polina Shurigina, Ekaterina Romanovskaya-Romanko, Kirill Vasilyev, Janna Buzitskaya |
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| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Tuberculosis Immunology Article M. tuberculosis multistage vaccine Mycobacterium tuberculosis 03 medical and health sciences influenza vector 0302 clinical medicine Immune system Antigen Immunity Drug Discovery Medicine Pharmacology (medical) 030212 general & internal medicine Pharmacology biology mucosal immunization business.industry HspX biochemical phenomena metabolism and nutrition Vector vaccine medicine.disease biology.organism_classification Virology 030104 developmental biology Infectious Diseases Immunization Nasal administration TB10.4 business |
| Zdroj: | Vaccines Vaccines, Vol 9, Iss 394, p 394 (2021) Volume 9 Issue 4 |
| ISSN: | 2076-393X |
| Popis: | New strategies providing protection against tuberculosis (TB) are still pending. The airborne nature of Mycobacterium tuberculosis (M.tb) infection assumes that the mucosal delivery of the TB vaccine could be a more promising strategy than the systemic route of immunization. We developed a mucosal TB vaccine candidate based on recombinant attenuated influenza vector (Flu/THSP) co-expressing truncated NS1 protein NS1(1–124) and a full-length TB10.4 and HspX proteins of M.tb within an NS1 protein open reading frame. The Flu/THSP vector was safe and stimulated a systemic TB-specific CD4+ and CD8+ T-cell immune response after intranasal immunization in mice. Double intranasal immunization with the Flu/THSP vector induced protection against two virulent M.tb strains equal to the effect of BCG subcutaneous injection in mice. In a guinea pig TB model, one intranasal immunization with Flu/THSP improved protection against M.tb when tested as a vaccine candidate for boosting BCG-primed immunity. Importantly, enhanced protection provided by a heterologous BCG-prime → Flu/THSP vector boost immunization scheme was associated with a significantly reduced lung and spleen bacterial burden (mean decrease of 0.77 lg CFU and 0.72 lg CFU, respectively) and improved lung pathology 8.5 weeks post-infection with virulent M.tb strain H37Rv. |
| Databáze: | OpenAIRE |
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