Objective:To evaluate the effects of primary anti-dengue virus envelop protein domain 3(DENV-ED3)antibodies on secondary heterotypic anti-DENV ED3 antibody responses and the status of anti-DENV antibody responses agai...Objective:To evaluate the effects of primary anti-dengue virus envelop protein domain 3(DENV-ED3)antibodies on secondary heterotypic anti-DENV ED3 antibody responses and the status of anti-DENV antibody responses against multivalent DENV ED3s in mice.Methods:Four different DENV-ED3s were purified and their biophysical characteristics were confirmed.Swiss albino mice aged 3-4 weeks were immunized with four different DENV-ED3s and the anti-ED3 IgG responses were determined by ELISA.Results:Firstly,the primary 1ED3-2ED3-3ED3 cross-reactive anti-DENV1 ED3 response boosted the secondary anti-2ED3 and anti-3ED3 antibody responses.In contrast,primary anti-2ED3 and anti-3ED3 antibodies neither had cross-recognition of 1ED3,nor had any effect on secondary anti-1ED3 response.Besides,the strict serospecificity of the anti-4ED3 sera did not affect other secondary anti-DENV ED3 responses.Secondly,1ED3,2ED3,and 3ED3 were co-dominantly immunogenic in trivalent ED3 formulations.However,the poorly immunogenic 4ED3 became almost non-immunogenic when injected after or together with 2ED3 and 3ED3,but showed slightly increased immunogenicity when injected with 1ED3,suggesting an adjuvanticity of 1ED3 on 4ED3’s immunogenicity.Conclusions:Although DENV1~4 ED3s share similar sequence homologies and structures,their immune induction potentials differ significantly in terms of immune magnitude,sero-specificity,and sero-cross-reactivity.Such intrinsic features of DENV1~4 ED3s may lead to‘antigen interference’,limiting both the understanding of dengue etiology and the success of dengue vaccine development,which needs to neutralize all four DENV serotypes equivalently.展开更多
Dear Editor,Dengue virus(DENV)is a positive-sense single-stranded RNA virus belonging to the Flaviviridae family,which causes dengue—a disease affecting over 400 million people annually worldwide.DENV is transmitted ...Dear Editor,Dengue virus(DENV)is a positive-sense single-stranded RNA virus belonging to the Flaviviridae family,which causes dengue—a disease affecting over 400 million people annually worldwide.DENV is transmitted through the bite of mosquitoes from the Aedes genus,primarily Aedes aegypti,and has a wide distribution in tropical and subtropical areas(de Souza et al.,2022).展开更多
Dengue virus(DENV)is a mosquito-borne virus with a rapid spread to humans,causing mild to potentially fatal illness in hundreds of millions of people each year.Due to the large number of serotypes of the virus,there r...Dengue virus(DENV)is a mosquito-borne virus with a rapid spread to humans,causing mild to potentially fatal illness in hundreds of millions of people each year.Due to the large number of serotypes of the virus,there remains an unmet need to develop protective vaccines for a broad spectrum of the virus.Here,we constructed a modified mRNA vaccine containing envelope domain III(E-DIII)and non-structural protein 1(NS1)coated with lipid nanoparticles.This multi-target vaccine induced a robust antiviral immune response and increased neutralizing antibody titers that blocked all four types of DENV infection in vitro without significant antibodydependent enhancement(ADE).In addition,there was more bias for Th1 than Th2 in the exact E-DIII and NS1-specific T cell responses after a single injection.Importantly,intramuscular immunization limited DENV transmission in vivo and eliminated vascular leakage.Our findings highlight that chimeric allogeneic structural and non-structural proteins can be effective targets for DENV vaccine and that they can prevent the further development of congenital DENV syndrome.展开更多
基金supported by a GARE-MOE,Bangladesh(Grant No.:LS201615)visiting scholar funding of GIR TUAT to M.M.I.Japanese government(Monbukagakusho:MEXT)Ph.D.scholarship to M.D.I.and S.Y.
文摘Objective:To evaluate the effects of primary anti-dengue virus envelop protein domain 3(DENV-ED3)antibodies on secondary heterotypic anti-DENV ED3 antibody responses and the status of anti-DENV antibody responses against multivalent DENV ED3s in mice.Methods:Four different DENV-ED3s were purified and their biophysical characteristics were confirmed.Swiss albino mice aged 3-4 weeks were immunized with four different DENV-ED3s and the anti-ED3 IgG responses were determined by ELISA.Results:Firstly,the primary 1ED3-2ED3-3ED3 cross-reactive anti-DENV1 ED3 response boosted the secondary anti-2ED3 and anti-3ED3 antibody responses.In contrast,primary anti-2ED3 and anti-3ED3 antibodies neither had cross-recognition of 1ED3,nor had any effect on secondary anti-1ED3 response.Besides,the strict serospecificity of the anti-4ED3 sera did not affect other secondary anti-DENV ED3 responses.Secondly,1ED3,2ED3,and 3ED3 were co-dominantly immunogenic in trivalent ED3 formulations.However,the poorly immunogenic 4ED3 became almost non-immunogenic when injected after or together with 2ED3 and 3ED3,but showed slightly increased immunogenicity when injected with 1ED3,suggesting an adjuvanticity of 1ED3 on 4ED3’s immunogenicity.Conclusions:Although DENV1~4 ED3s share similar sequence homologies and structures,their immune induction potentials differ significantly in terms of immune magnitude,sero-specificity,and sero-cross-reactivity.Such intrinsic features of DENV1~4 ED3s may lead to‘antigen interference’,limiting both the understanding of dengue etiology and the success of dengue vaccine development,which needs to neutralize all four DENV serotypes equivalently.
文摘Dear Editor,Dengue virus(DENV)is a positive-sense single-stranded RNA virus belonging to the Flaviviridae family,which causes dengue—a disease affecting over 400 million people annually worldwide.DENV is transmitted through the bite of mosquitoes from the Aedes genus,primarily Aedes aegypti,and has a wide distribution in tropical and subtropical areas(de Souza et al.,2022).
基金supported by the Strategic Priority Research Program of CAS (XDB29010000)partially financially supported by the Institute of Infectious Disease of Shenzhen Bay Laboratorysupported by the Youth Innovation Promotion Association of CAS (2019091)
文摘Dengue virus(DENV)is a mosquito-borne virus with a rapid spread to humans,causing mild to potentially fatal illness in hundreds of millions of people each year.Due to the large number of serotypes of the virus,there remains an unmet need to develop protective vaccines for a broad spectrum of the virus.Here,we constructed a modified mRNA vaccine containing envelope domain III(E-DIII)and non-structural protein 1(NS1)coated with lipid nanoparticles.This multi-target vaccine induced a robust antiviral immune response and increased neutralizing antibody titers that blocked all four types of DENV infection in vitro without significant antibodydependent enhancement(ADE).In addition,there was more bias for Th1 than Th2 in the exact E-DIII and NS1-specific T cell responses after a single injection.Importantly,intramuscular immunization limited DENV transmission in vivo and eliminated vascular leakage.Our findings highlight that chimeric allogeneic structural and non-structural proteins can be effective targets for DENV vaccine and that they can prevent the further development of congenital DENV syndrome.
