Chronic hepatitis B(CHB)is consistently challenging to conquer with numerous complications and fatalities.Despite the effectiveness of antiviral therapies in suppressing hepatitis B virus(HBV)replication,there is an u...Chronic hepatitis B(CHB)is consistently challenging to conquer with numerous complications and fatalities.Despite the effectiveness of antiviral therapies in suppressing hepatitis B virus(HBV)replication,there is an urgent need for novel and more effective treatment modalities.Current strategies predominantly emphasize immune activation but still face challenges in sufficiently eliciting T cell responses.Taking into account the targeted delivery of nanoparticles to the liver and spleen via intravenous injection,we have proposed a dual-pronged therapeutic strategy based on antigen-presenting cells(APCs)-derived exosomes.Specifically,exosomes targeted to the spleen can activate specific immune responses,while those targeted to the liver can modulate or reverse the liver’s immunosuppressive microenvironment.After immunization,exosome formulations exhibit the remarkable ability to effectively activate APCs,thereby triggering the proliferation of CD8^(+)T cells.Simultaneously,they also play an immunoregulatory role by converting M2 macrophages into M1 macrophages.This two-pronged therapeutic strategy precisely addresses the issues of T cell dysfunction and immune suppression,both characteristic features of CHB patients.When combined with Aluminum(Alum)-adjuvanted vaccine,these exosome formulations not only demonstrate a high level of cellular immune response but also secrete specific antibodies comparable to those induced by Alum adjuvant.This combined approach effectively enhances both cellular and humoral immunity,offering a promising avenue for the development of therapeutic hepatitis B vaccines based on exosome formulations.展开更多
基金supported by National Key Research and Development Program of China(Nos.2023YFC2307704,and 2021YFC2302603)National Natural Science Foundation of China(Nos.82341405,and 32030062)+1 种基金CAS Project for Young Scientists in Basic Research(No.YSBR-083)IPE Project for Frontier Basic Research(No.QYJC-2022-012).
文摘Chronic hepatitis B(CHB)is consistently challenging to conquer with numerous complications and fatalities.Despite the effectiveness of antiviral therapies in suppressing hepatitis B virus(HBV)replication,there is an urgent need for novel and more effective treatment modalities.Current strategies predominantly emphasize immune activation but still face challenges in sufficiently eliciting T cell responses.Taking into account the targeted delivery of nanoparticles to the liver and spleen via intravenous injection,we have proposed a dual-pronged therapeutic strategy based on antigen-presenting cells(APCs)-derived exosomes.Specifically,exosomes targeted to the spleen can activate specific immune responses,while those targeted to the liver can modulate or reverse the liver’s immunosuppressive microenvironment.After immunization,exosome formulations exhibit the remarkable ability to effectively activate APCs,thereby triggering the proliferation of CD8^(+)T cells.Simultaneously,they also play an immunoregulatory role by converting M2 macrophages into M1 macrophages.This two-pronged therapeutic strategy precisely addresses the issues of T cell dysfunction and immune suppression,both characteristic features of CHB patients.When combined with Aluminum(Alum)-adjuvanted vaccine,these exosome formulations not only demonstrate a high level of cellular immune response but also secrete specific antibodies comparable to those induced by Alum adjuvant.This combined approach effectively enhances both cellular and humoral immunity,offering a promising avenue for the development of therapeutic hepatitis B vaccines based on exosome formulations.
