Abstract
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.
Highlights
IntroductionAccording to the WHO global tuberculosis report, TB remains one of the top 10 causes of death worldwide
We investigate the innate and adaptive immune response in mice immunized with recombinant influenza A/PR/8/34 strain, expressing a hybrid molecule consisting of mycobacterial antigens TB.10.4 and HspX
The protective efficacy of anti-tuberculosis immune response is largely dependent on Th1-polarised CD4+ T-cells and CD8+ CTLs [32,33,34,35,36]
Summary
According to the WHO global tuberculosis report, TB remains one of the top 10 causes of death worldwide. A great variety of tuberculosis vaccine candidates is at different stages of clinical efficacy trials, including whole cell-derived vaccines (killed or attenuated through genetic modifications), subunit and recombinant viral-vectored vaccines (reviewed in [1,2,3]). The only approved TB vaccine, Bacille Calmette–Guérin (BCG) is widely used with the coverage of about 90% in 120 countries providing BCG vaccination (WHO, Geneva, Switzerland, 2018). The effectiveness of BCG in preventing the disease is restricted by early childhood and does not exceed 50% (WHO, Geneva, Switzerland, 2013). Improving the techniques of specific tuberculosis prevention remains one of the priorities of phthisiology The effectiveness of BCG in preventing the disease is restricted by early childhood and does not exceed 50% (WHO, Geneva, Switzerland, 2013). 4.0/).
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