TB Research

The Profile of T Cell Responses in Bacille Calmette-Guérin-Primed Mice Boosted by a Novel Sendai Virus Vectored Anti-Tuberculosis Vaccine

Hu Z, Gu L, Li CL, Shu T, Lowrie DB, Fan XY

Frontiers in immunology · 2018-08

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.

MeSH terms

  • Lung
  • Spleen
  • T-Lymphocyte Subsets
  • Animals
  • Mice
  • Mycobacterium tuberculosis
  • Sendai virus
  • Tuberculosis
  • Disease Models, Animal
  • Tuberculosis Vaccines
  • BCG Vaccine
  • Antigens, Bacterial
  • Cytokines
  • Immunization, Secondary
  • Immunity, Cellular
  • Immunologic Memory
  • Genetic Vectors
  • Female