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Efficient control of chronic LCMV infection by a CD4 T cell epitope-based heterologous prime-boost vaccination in a murine model

查看全文 作　　者：Ran [1,2]He;Xinxin [2]Yang;Cheng [2]Liu;Xiangyu [2]Chen;Lin [2]Wang;Minglu [2]Xiao;Jianqiang [3,4]Ye;Yuzhang [1,2]Wu;Lilin [2]Ye 高影响力作者 机构地区：[1]Center for Clinical Laboratory,Zhujiang Hospital,Southern Medical University,Guangzhou 510515,China;[2]Institute of Immunology,Medical School,Third Military Medical University,Chongqing 400038,China;[3]Ministry of Education Key Laboratory for Avian Preventive Medicine,College of Veterinary Medicine,Yangzhou University,Yangzhou,Jiangsu 225009,China;[4]Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses,Yangzhou,Jiangsu 225009,China高影响力机构 出　　处：《Cellular & Molecular Immunology》索引2018年第15卷第9期,共12页高影响力期刊 基　　金：The work was supported by National Basic Research Program of China(973 program,2013CB531500,to LY);the National Natural Science Foundation of China(81471624 to LY). 摘　　要：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 virusspecific 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. 关 键 词：CD4^(+)T cell epitope CD8^(+)T cell exhaustion chronic viral infection PRIME-BOOST
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