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Article

Mucosal Influenza Vector Vaccine Carrying TB10.4 and HspX Antigens Provides Protection against Mycobacterium tuberculosis in Mice and Guinea Pigs

1
Smorodintsev Research Institute of Influenza of the Ministry of Health of the Russian Federation, 197376 St. Petersburg, Russia
2
Saint-Petersburg State Research Institute of Phthisiopulmonology of the Ministry of Health of the Russian Federation, 191036 St. Petersburg, Russia
3
Peter The Great St. Petersburg Polytechnic University, 195251 St. Petersburg, Russia
*
Author to whom correspondence should be addressed.
Academic Editors: Maria G. Isaguliants and Felicity Jane Burt
Vaccines 2021, 9(4), 394; https://doi.org/10.3390/vaccines9040394
Received: 16 March 2021 / Revised: 12 April 2021 / Accepted: 14 April 2021 / Published: 16 April 2021
(This article belongs to the Special Issue Perspective Technologies of Vaccination and Immunotherapy)
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. View Full-Text
Keywords: M. tuberculosis multistage vaccine; TB10.4; HspX; influenza vector; mucosal immunization M. tuberculosis multistage vaccine; TB10.4; HspX; influenza vector; mucosal immunization
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MDPI and ACS Style

Sergeeva, M.; Romanovskaya-Romanko, E.; Zabolotnyh, N.; Pulkina, A.; Vasilyev, K.; Shurigina, A.P.; Buzitskaya, J.; Zabrodskaya, Y.; Fadeev, A.; Vasin, A.; Vinogradova, T.I.; Stukova, M.A. Mucosal Influenza Vector Vaccine Carrying TB10.4 and HspX Antigens Provides Protection against Mycobacterium tuberculosis in Mice and Guinea Pigs. Vaccines 2021, 9, 394. https://doi.org/10.3390/vaccines9040394

AMA Style

Sergeeva M, Romanovskaya-Romanko E, Zabolotnyh N, Pulkina A, Vasilyev K, Shurigina AP, Buzitskaya J, Zabrodskaya Y, Fadeev A, Vasin A, Vinogradova TI, Stukova MA. Mucosal Influenza Vector Vaccine Carrying TB10.4 and HspX Antigens Provides Protection against Mycobacterium tuberculosis in Mice and Guinea Pigs. Vaccines. 2021; 9(4):394. https://doi.org/10.3390/vaccines9040394

Chicago/Turabian Style

Sergeeva, Mariia, Ekaterina Romanovskaya-Romanko, Natalia Zabolotnyh, Anastasia Pulkina, Kirill Vasilyev, Anna P. Shurigina, Janna Buzitskaya, Yana Zabrodskaya, Artem Fadeev, Andrey Vasin, Tatiana I. Vinogradova, and Marina A. Stukova 2021. "Mucosal Influenza Vector Vaccine Carrying TB10.4 and HspX Antigens Provides Protection against Mycobacterium tuberculosis in Mice and Guinea Pigs" Vaccines 9, no. 4: 394. https://doi.org/10.3390/vaccines9040394

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