Efficient control of chronic LCMV infection by a CD4 T cell epitope-based heterologous prime-boost vaccination in a murine model. Issue 9 (September 2018)

• Record Type: Journal Article
• Authors: He, Ran; Yang, Xinxin; Liu, Cheng; Chen, Xiangyu; Wang, Lin; Xiao, Minglu; Ye, Jianqiang; Wu, Yuzhang; Ye, Lilin
• Is Part Of: Cellular & molecular immunology. Volume 15:Issue 9(2018)
• Page Start: 815
• Page End: 826
• Publication Date: 2018-09
• Subjects: CD4+ T cell epitope -- CD8+ T cell exhaustion -- chronic viral infection -- prime-boost; Immunology -- Periodicals; Cellular immunity -- Periodicals; Molecular biology -- Periodicals; 616.079
• DOI: 10.1038/cmi.2017.3
• Languages: English
• ISSNs: 1672-7681

Abstract

Abstract CD4+ T cells are essential for sustaining CD8+ T cell responses during a chronic infection. The adoptive transfer of virus-specific CD4+ T cells has been shown to efficiently rescue exhausted CD8+ T cells. However, the question of whether endogenous virus-specific CD4+ T cell responses can be enhanced by certain vaccination strategies and subsequently reinvigorate exhausted CD8+ T cells remains unexplored. In this study, we developed a CD4+ T cell epitope-based heterologous prime-boost immunization strategy and examined the efficacy of this strategy using a mouse model of chronic lymphocytic choriomeningitis virus (LCMV) infection. We primed chronically LCMV-infected mice with aListeria monocytogenes vector that expressed the LCMV glycoprotein-specific I-Ab -restricted CD4+ T cell epitope GP61–80 (LM-GP61) and subsequently boosted the primed mice with an influenza virus A (PR8 strain) vector that expressed the same CD4+ T cell epitope (IAV-GP61). This heterologous prime-boost vaccination strategy elicited strong anti-viral CD4+ T cell responses, which further improved both the quantity and quality of the virus-specific CD8+ T cells and led to better control of the viral loads. The combination of this strategy and the blockade of the programmed cell death-1 (PD-1) inhibitory pathway further enhanced the anti-viral CD8+ T cell responses and viral clearance. Thus, a heterologous prime-boost immunization that selectively induces virus-specific CD4+ T cell responses in conjunction with blockade of the inhibitory pathway may represent a promising therapeutic approach to treating patients with chronic viral infections.