Abstract
The kinds of vaccine-induced T cell responses that are beneficial for protection against Mycobacterium tuberculosis (Mtb) infection are not adequately defined. We had shown that a novel Sendai virus vectored vaccine, SeV85AB, was able to enhance immune protection induced by bacille Calmette–Guérin (BCG) in a prime-boost model. However, the profile of T cell responses boosted by SeV85AB was not determined. Herein, we show that the antigen-specific CD4+ and CD8+ T cell responses were both enhanced by the SeV85AB boost after BCG. Different profiles of antigen-specific po T cell subsets were induced in the local (lung) and systemic (spleen) sites. In the spleen, the CD4+ T cell responses that were enhanced by the SeV85AB boost were predominately IL-2 responses, whereas in the lung the greater increases were in IFN-γ- and TNF-α-producing CD4+ T cells; in CD8+ T cells, although IFN-γ was enhanced in both the spleen and lung, only IL-2+TNF-α+CD8+ T subset was boosted in the latter. After a challenge Mtb infection, there were significantly higher levels of recall IL-2 responses in T cells. In contrast, IFN-γ-producing cells were barely boosted by SeV85AB. After Mtb challenge a central memory phenotype of responding CD4+ T cells was a prominent feature in SeV85AB-boosted mice. Thus, our data strongly suggest that the enhanced immune protection induced by SeV85AB boosting was associated with establishment of an increased capacity to recall antigen-specific IL-2-mediated T cell responses and confirms this Sendai virus vector system as a promising candidate to be used in a heterologous prime-boost immunization regimen against TB.
Highlights
Tuberculosis (TB) remains among the most deadly health challenge to humankind
PPD-specific cell responses were only slightly induced by SeV85AB, mice receiving SeV85AB boost secreted higher levels of IFN-γ compared with SeV85AB or bacille Calmette–Guérin (BCG) single immunization (Figures 1C,D)
Ag85AB peptide pool or incubated with medium as control (The gating strategy is shown in Figure S1 in Supplementary Material, CD4+ T cells were gated as CD3+CD4+ cells and CD8+ T cells were defined as CD3+CD4− cells) and the results of flow cytometric
Summary
Bacille Calmette– Guérin (BCG), the attenuated form of Mycobacterium bovis, has been used for over 80 years to protect children against severe forms of TB [1]. T Cell Responses by BCG Prime-SeV85AB Boost. T cell responses are regarded as a critical factor in containment of Mycobacterium tuberculosis (Mtb) infection. During the course of Mtb-driven differentiation, the T cells can gain the capacity to simultaneously produce two or more key cytokines and are called poly-functional T cells, which are considered to be superior effectors of protective immunity as compared to cells that produce only one cytokine [4]. IFN-γ, IL-2, and TNF-α secreting CD4+ T cells, which are known as Th1 cells, are regarded as crucial for activation of effector functions to control intracellular Mtb and are correlated with protection [5, 6]
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