Document Type
Article
Publication Date
1-31-2014
Description
In this study, we engineered Listeria monocytogens (Lm) by deleting the LmΔactA/ΔinlB virulence determinants and inserting HCV-NS5B consensus antigens to develop a therapeutic vaccine against hepatitis C virus (HCV) infection. We tested this recombinant Lm-HCV vaccine in triggering of innate and adaptive immune responses in vitro using immune cells from HCV-infected and uninfected individuals. This live-attenuated Lm-HCV vaccine could naturally infect human dendritic cells (DC), thereby driving DC maturation and antigen presentation, producing Th1 cytokines, and triggering CTL responses in uninfected individuals. However, vaccine responses were diminished when using DC and T cells derived from chronically HCV-infected individuals, who express higher levels of inhibitory molecule Tim-3 on immune cells. Notably, blocking Tim-3 signaling significantly improved the innate and adaptive immune responses in chronically HCV-infected patients, indicating that novel strategies to enhance the potential of antigen presentation and cellular responses are essential for developing an effective therapeutic vaccine against HCV infection.
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.
Citation Information
Ma, Cheng J.; Ren, Jun P.; Li, Guang Y.; Wu, Xiao Y.; Brockstedt, Dirk G.; Lauer, Peter; Moorman, Jonathan P.; and Yao, Zhi Q.. 2014. Enhanced Virus-Specific CD8+ T Cell Responses by Listeria Monocytogenes-Infected Dendritic Cells in the Context of Tim-3 Blockade. PLoS ONE. Vol.9(1). https://doi.org/10.1371/journal.pone.0087821 PMID: 24498204
Copyright Statement
This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.