Enhancement of the Local CD8 + T-Cellular Immune Response to Mycobacterium tuberculosis in BCG-Primed Mice after Intranasal Administration of Influenza Vector Vaccine Carrying TB10.4 and HspX Antigens.

Autor: Vasilyev K; Smorodintsev Research Institute of Influenza of the Ministry of Health of the Russian Federation, 197376 St. Petersburg, Russia., Shurygina AP; Smorodintsev Research Institute of Influenza of the Ministry of Health of the Russian Federation, 197376 St. Petersburg, Russia., Zabolotnykh N; Saint-Petersburg State Research Institute of Phthisiopulmonology of the Ministry of Health of the Russian Federation, 191036 St. Petersburg, Russia., Sergeeva M; Smorodintsev Research Institute of Influenza of the Ministry of Health of the Russian Federation, 197376 St. Petersburg, Russia., Romanovskaya-Romanko E; Smorodintsev Research Institute of Influenza of the Ministry of Health of the Russian Federation, 197376 St. Petersburg, Russia., Pulkina A; Smorodintsev Research Institute of Influenza of the Ministry of Health of the Russian Federation, 197376 St. Petersburg, Russia., Buzitskaya J; Smorodintsev Research Institute of Influenza of the Ministry of Health of the Russian Federation, 197376 St. Petersburg, Russia., Dogonadze MZ; Saint-Petersburg State Research Institute of Phthisiopulmonology of the Ministry of Health of the Russian Federation, 191036 St. Petersburg, Russia., Vinogradova TI; Saint-Petersburg State Research Institute of Phthisiopulmonology of the Ministry of Health of the Russian Federation, 191036 St. Petersburg, Russia., Stukova MA; Smorodintsev Research Institute of Influenza of the Ministry of Health of the Russian Federation, 197376 St. Petersburg, Russia.
Jazyk: angličtina
Zdroj: Vaccines [Vaccines (Basel)] 2021 Nov 03; Vol. 9 (11). Date of Electronic Publication: 2021 Nov 03.
DOI: 10.3390/vaccines9111273
Abstrakt: BCG is the only licensed vaccine against Mycobacterium tuberculosis (M.tb) infection. Due to its intramuscular administration route, BCG is unable to induce a local protective immune response in the respiratory system. Moreover, BCG has a diminished ability to induce long-lived memory T-cells which are indispensable for antituberculosis protection. Recently we described the protective efficacy of new mucosal TB vaccine candidate based on recombinant attenuated influenza vector (Flu/THSP) co-expressing TB10.4 and HspX proteins of M.tb within an NS1 influenza protein open reading frame. In the present work, the innate and adaptive immune response to immunization with the Flu/THSP and the immunological properties of vaccine candidate in the BCG-prime → Flu/THSP vector boost vaccination scheme are studied in mice. It was shown that the mucosal administration of Flu/THSP induces the incoming of interstitial macrophages in the lung tissue and stimulates the expression of co-stimulatory CD86 and CD83 molecules on antigen-presenting cells. The T-cellular immune response to Flu/THSP vector was mediated predominantly by the IFNγ-producing CD8 + lymphocytes. BCG-prime → Flu/THSP vector boost immunization scheme was shown to protect mice from severe lung injury caused by M.tb infection due to the enhanced T-cellular immune response, mediated by antigen-specific effector and central memory CD4 + and CD8 + T-lymphocytes.
Databáze: MEDLINE