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

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-Guerin (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-gamma- and TNF-alpha-producing CD4(+) T cells; in CD8(+) T cells, although IFN-gamma was enhanced in both the spleen and lung, only IL-2(+) TNF-alpha+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-gamma 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