title: Efficient control of chronic LCMV infection by a CD4 T cell epitope-based heterologous prime-boost vaccination in a murine model.
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 a Listeria 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.
authors.affiliation: Center for Clinical Laboratory, Zhujiang Hospital, Southern Medical University, 510515, Guangzhou, China.|Institute of Immunology, Medical School, Third Military Medical University, 400038, Chongqing, China.
authors.forename: Ran
authors.initials: R
authors.lastname: He
authors.affiliation: Institute of Immunology, Medical School, Third Military Medical University, 400038, Chongqing, China.
authors.forename: Xinxin
authors.initials: X
authors.lastname: Yang
authors.affiliation: Institute of Immunology, Medical School, Third Military Medical University, 400038, Chongqing, China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Liu
authors.affiliation: Institute of Immunology, Medical School, Third Military Medical University, 400038, Chongqing, China.
authors.forename: Xiangyu
authors.initials: X
authors.lastname: Chen
authors.affiliation: Institute of Immunology, Medical School, Third Military Medical University, 400038, Chongqing, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Wang
authors.affiliation: Institute of Immunology, Medical School, Third Military Medical University, 400038, Chongqing, China.
authors.forename: Minglu
authors.initials: M
authors.lastname: Xiao
authors.affiliation: Ministry of Education Key Laboratory for Avian Preventive Medicine, College of Veterinary Medicine, Yangzhou University, 225009, Yangzhou, China, Jiangsu.|Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, 225009, Yangzhou, China, Jiangsu.
authors.forename: Jianqiang
authors.initials: J
authors.lastname: Ye
authors.affiliation: Center for Clinical Laboratory, Zhujiang Hospital, Southern Medical University, 510515, Guangzhou, China.|Institute of Immunology, Medical School, Third Military Medical University, 400038, Chongqing, China.
authors.forename: Yuzhang
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Institute of Immunology, Medical School, Third Military Medical University, 400038, Chongqing, China. yelilinlcmv@tmmu.edu.cn.
authors.forename: Lilin
authors.initials: L
authors.lastname: Ye
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes; D002908:Chronic Disease; D018984:Epitopes, T-Lymphocyte / Q000235:genetics / Q000276:immunology; D005822:Genetic Vectors; D007117:Immunization, Secondary; D009980:Influenza A virus; D008089:Listeria monocytogenes; D008216:Lymphocytic Choriomeningitis / Q000235:genetics / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D008217:Lymphocytic choriomeningitis virus / Q000235:genetics / Q000276:immunology*; D051379:Mice
chemical_list: D018984:Epitopes, T-Lymphocyte
keywords: CD4+ T cell epitope; CD8+ T cell exhaustion; chronic viral infection; prime-boost