| Chronic hepatitis B virus infection which is the highest prevalence of chronic viral infections in the world lacks effective cures currently.Nowadays,Anti-HBV is mainly used clinically with interferon a(IFN-a)and/or nucleos(t)ide analogues(NAs).Both drugs can effectively inhibit the replication of HBV virus and control disease progression,but only in a very few patients achieved clinical cure(HBsAg negative conversion).Current studies have shown that high levels of HBsAg in chronic hepatitis B infection may be an important cause of host immune tolerance,so studies of novel anti-HBV drugs should effectively reduce HBsAg in patients and help the recovery of host immune responses to HBV.In the previous study,our team found an antibody named E6F6 that can effectively eliminate HBV in the HBV mouse model and successfully identified its epitope that is HBsAg aal 19-125.The peptide SEQ13(HBsAg aa113-135)with this epitope was displayed on a virus-like particle carrier,a novel epitope chimeric therapeutic hepatitis B vaccine named CR-T3-SEQ13 was constructed.We have demonstrated in a variety of animal models that the vaccine has a significant anti-HBV therapeutic effect,good immunogenicity and safety.However,there is currently a lack of therapeutic strategies for CR-T3-SEQ13 vaccine in mouse models.This study aimed to optimize the treatment strategies for CR-T3-SEQ13 vaccine in mouse models,including optimization of immunization procedures and the combination therapy between IFN or NAs,and the antibodies produced by the CR-T3-SEQ13 vaccine immunity were analyzed and identified to determine the epitopes of the antibodies induced by CR-T3-SEQ13 vaccine.This study mainly includes four parts of the research content.The first part of the study focused on the immunization procedure for the CR-T3-SEQ13 therapeutic vaccine.The efficacy of one dose of weekly immunization and one dose of two weeks immunization was evaluated in a HBV transgenic mice and the results showed no significant difference.The second part of the study was the use of the CR-T3-SEQ13 vaccine in combination with anti-HBV drug nucleoside analogues(entecavir and tenofovir)or interferon a and the results showed that the use of nucleoside analogues and interferon a will not Significantly affect the therapeutic effect of therapeutic vaccines.The third part was the use of the therapeutic antibody 129G1(a murine monoclonal antibody against the HBsAg aa137-151 epitope that has been shown to have therapeutic efficacy against HBV)in combination with the CR-T3-SEQ13 vaccine.The 129G1 can significantly enhance the immune response of CR-T3-SEQ13 vaccine in female mice.The fourth part focuses on the property analysis of antibodies induced after CR-T3-SEQ13 vaccine immunization in mice.BALB/c mice were immunized with the CR-T3-SEQ13 vaccine.A total of 14 monoclonal antibodies specific for the SEQ13 epitope were prepared.Epitope analysis revealed that these antibodies mainly recognize the binding epitope of the sA epitope(HBsAg-aa121-124).In summary,this study used a hepatitis B mouse model to explore therapeutic strategies for the novel epitope chimeric therapeutic vaccine CR-T3-SEQ13.The results of the study showed that the CR-T3-SEQ13 vaccine can combined with IFN-α、NAs and the therapeutic antibody 129G1,and the CR-T3-SEQ13 vaccine induces antibodies specific for chimeric epitopes in mice.These findings will provide a scientific basis and guidance for the optimal design of CR-T3-SEQ13 vaccines in further clinical treatment trials and strategies. |
PDF Full Text Request