Current seasonal influenza vaccines confer only limited coverage of virus strains due to the frequent genetic and antigenic variability of influenza virus(IV).Epitope vaccines that accurately target conserved domains ...Current seasonal influenza vaccines confer only limited coverage of virus strains due to the frequent genetic and antigenic variability of influenza virus(IV).Epitope vaccines that accurately target conserved domains provide a promising approach to increase the breadth of protection;however,poor immunogenicity greatly hinders their application.The protruding(P)domain of the norovirus(NoV),which can self-assemble into a 24-mer particle called the NoV P particle,offers an ideal antigen presentation platform.In this study,a multiepitope nanovaccine displaying influenza epitopes(HMN-PP)was constructed based on the NoV P particle nanoplatform.Large amounts of HMN-PP were easily expressed in Escherichia coli in soluble form.Animal experiments showed that the adjuvanted HMN-PP nanovaccine induced epitope-specific antibodies and haemagglutinin(HA)-specific neutralizing antibodies,the antibodies could persist for at least three months after the last immunization.Furthermore,HMN-PP induced matrix protein 2 extracellular domain(M2e)-specific antibody-dependent cell-mediated cytotoxicity,CD4^(+)and CD8^(+)T-cell responses,a nucleoprotein(NP)-specific cytotoxic T lymphocyte(CTL)response.These results indicated that the combination of a multiepitope vaccine and self-assembled NoV P particles may be an ideal and effective vaccine strategy for highly variable viruses such as IV and SARS-CoV-2.展开更多
基金the Department of Science and Technology of Jilin Province(Nos.20220204008YY and 20210204197YY)Changchun Science and Technology Bureau(No.21ZY15).
文摘Current seasonal influenza vaccines confer only limited coverage of virus strains due to the frequent genetic and antigenic variability of influenza virus(IV).Epitope vaccines that accurately target conserved domains provide a promising approach to increase the breadth of protection;however,poor immunogenicity greatly hinders their application.The protruding(P)domain of the norovirus(NoV),which can self-assemble into a 24-mer particle called the NoV P particle,offers an ideal antigen presentation platform.In this study,a multiepitope nanovaccine displaying influenza epitopes(HMN-PP)was constructed based on the NoV P particle nanoplatform.Large amounts of HMN-PP were easily expressed in Escherichia coli in soluble form.Animal experiments showed that the adjuvanted HMN-PP nanovaccine induced epitope-specific antibodies and haemagglutinin(HA)-specific neutralizing antibodies,the antibodies could persist for at least three months after the last immunization.Furthermore,HMN-PP induced matrix protein 2 extracellular domain(M2e)-specific antibody-dependent cell-mediated cytotoxicity,CD4^(+)and CD8^(+)T-cell responses,a nucleoprotein(NP)-specific cytotoxic T lymphocyte(CTL)response.These results indicated that the combination of a multiepitope vaccine and self-assembled NoV P particles may be an ideal and effective vaccine strategy for highly variable viruses such as IV and SARS-CoV-2.
