Efficient Control Of Chronic LCMV Infection By A CD4 T Cell Epitope-based Heterologous Prime-boost Vaccination In A Murine Model

During chronic viral infection,CD4~+ T cells play critical roles in maintaining CD8~+ T cell immune response.Previous studies have revealed that adoptive transfer of virus-specific CD4~+ T cells co?ld rescue the function of exhausted CD8~+ T cells efficiently in chronic infection.However,whether certain vaccination strategies co?ld improve the virus-specific immune response of endogenous CD4~+ T cells and subsequently revival exhausted CD8~+ T cell response remains unexplored.This study established a CD4~+ T cell epitope-based heterologous prime-boost immunization strategy and used a typical mouse chronic viral infection model-lymphocytic choriomeningitis virus(LCMV)infection to examine the efficiency of this strategy.The chronically LCMV-infected mice were primed by a Listeria monocytogenes vector expressing the LCMV glycoprotein-specific I-Ab-restricted CD4~+ T cell epitope GP61-80(LM-GP61)firstly and then boosted by an influenza virus A(PR8 strain)vector that express the same CD4~+ T cell epitope(IAV-GP61).The prime-boost strategy described in this study excite a strong anti-viral CD4~+ T cell response and further improved both the number and function of virus-specific CD8~+ T cells,which led to a better control of viral replication in chronic infection.The prime-boost immunization strategy further improved the anti-viral CD8~+ T cell response when combined with anti-PD-L1 treatment.Therefore,the CD4~+ T cell epitope-based heterologous prime-boost immunization that significantly induces virus-specific CD4~+ T cell responses combined with inhibitory pathway blockade may shed new light on treating chronic viral infected patients.