A Promising Listeria-Vectored Vaccine Induces Th1-Type Immune Responses and Confers Protection Against Tuberculosis

摘要

Tuberculosis (TB) continues to kill 1.4 million people annually, numbers of patients with drug-resistant tuberculosis increases alamingly. The vaccine is an important medical intervention in TB prevention strategies, only Bacilli Calmette-Guerin (BCG) is approved worldwide for clinical use, it is not ideally for the protection of teenagers or adults. Therefore, alternative effective and safe vaccine is urgently needed. In this study, we designed a novel vaccine by using an attenuated Listeria monocytogenes (LM) strain carrying fusion antigen FbpB-ESAT-6 (rLM) and characterized its safety and protective efficacy against Mycobacterium tuberculosis (M.tb) infection in mice. Compared to the wild type strain yzuLM4 and parental strain yzuLM4LMΔactA/plcB (LM1-2), the virulence of rLM was significantly reduced as judged by its infectious kinetics and LD50. Further characterization of intravenous immunization showed that prime-boost vaccination significantly increased the levels of Th1 cytokine (IFN-γ, IL-17 and IL-6), enhanced CTLs activity, suggesting that rLM could remarkably elicit both Th1 -biased cellular responses. More importantly, rLM significantly enhanced the protection against M. tuberculosis H37Rv challenge. Collectively, our findings indicated that rLM is a novel and useful tool to prevent M.tb infection, and can be potentially used to boost BCG-primed immunity.