Pyrazinamide enhances persistence of T-cell memory induced by tuberculosis subunit vaccine LT70

Abstract

Repurposing anti-tuberculosis drugs with adjuvant properties in vaccination has double benefits for the control of tuberculosis. In this study, to verify the immunomodulatory effect of the tuberculosis drug pyrazinamide (PZA) on tuberculosis subunit vaccine-induced memory T cell response, we treated mice with PZA during the course of vaccination and then monitored the vaccine-specific T cell memory responses. Compared with the mice that received LT70 alone, we found that the mice co-administrated with PZA and LT70 did not produce a higher frequency of multifunctional CD4+ T lymphocytes at 8-week post-vaccination, but the T lymphocytes produced stronger long-term IL-2 response rather than IFN-γ recall response and had higher long-term proliferating potential upon antigen stimulation at 28-week post-vaccination. In addition, the memory T cells from PZA-treated mice showed superior IFN-γ recall response after twice antigen stimulations in vivo and in vitro respectively. Together, the findings show that PZA treatment during the course of vaccination contributes to inducing TCM-like cells and enhances vaccine-induced T-cell long-term immunological memory, which would be helpful for designing novel vaccination and therapeutic strategies for tuberculosis.