Objectives： The aim was to construct 2009 pandemic A/HINI influenza VLPs （virus-like particles） and compare the immunogenicity and protection efficacy with the commercial Panenza vaccine in BALB/c mouse model. Meth...Objectives： The aim was to construct 2009 pandemic A/HINI influenza VLPs （virus-like particles） and compare the immunogenicity and protection efficacy with the commercial Panenza vaccine in BALB/c mouse model. Methods： VLPs derived from influenza A/Hong Kong/01/2009 （H 1N 1 ） virus were constructed by Bac-to-Bac baculovirus expression system. VLPs were purified by sucrose density gradient ultracentrifugation and then characterized by Western blotting analysis and transmission electron microscopy. After single dose vaccination with 3 lag of VLPs and equal amount of Panenza vaccine, the immune responses and efficacy of protection induced by VLPs were compared with those elicited by the Panenza vaccine in 6-8 weeks old female BALB/c mice. Key findings： VLPs could induce higher antibody titer as determined by hemagglutinin inhibition and microneutralization assay. Furthermore, we demonstrated that VLPs induced better antibody response to neuraminidase. In addition, VLP vaccinated mice had stronger cell-mediated immune response. As a result, our VLPs conferred 100% protection while the Panenza vaccine only conferred 67% protection. Conclusion： From the results, we concluded that influenza VLPs are highly immunogenic and they are promising to be developed as an alternative strategy to vaccine production in order to control the spread of influenza viruses.展开更多
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
文摘Objectives： The aim was to construct 2009 pandemic A/HINI influenza VLPs （virus-like particles） and compare the immunogenicity and protection efficacy with the commercial Panenza vaccine in BALB/c mouse model. Methods： VLPs derived from influenza A/Hong Kong/01/2009 （H 1N 1 ） virus were constructed by Bac-to-Bac baculovirus expression system. VLPs were purified by sucrose density gradient ultracentrifugation and then characterized by Western blotting analysis and transmission electron microscopy. After single dose vaccination with 3 lag of VLPs and equal amount of Panenza vaccine, the immune responses and efficacy of protection induced by VLPs were compared with those elicited by the Panenza vaccine in 6-8 weeks old female BALB/c mice. Key findings： VLPs could induce higher antibody titer as determined by hemagglutinin inhibition and microneutralization assay. Furthermore, we demonstrated that VLPs induced better antibody response to neuraminidase. In addition, VLP vaccinated mice had stronger cell-mediated immune response. As a result, our VLPs conferred 100% protection while the Panenza vaccine only conferred 67% protection. Conclusion： From the results, we concluded that influenza VLPs are highly immunogenic and they are promising to be developed as an alternative strategy to vaccine production in order to control the spread of influenza viruses.
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.
