Anti-DENV-ED3 antibody cross-talks generate immune interference among the four DENVs  

作　　者：Md.Din Islam Sanjida Yesmin Tahmina Sharmin Md.Ayoub Khan Yutaka Kuroda M.Monirul Islam 

机构地区：[1]Department of Biotechnology and Life Science,Faculty of Engineering,Tokyo University of Agriculture and Technology,2-24-16 Nakamachi,Koganei-shi,Tokyo 184-8588,Japan [2]Department of Biochemistry and Molecular Biology,Faculty of Biological Sciences,University of Chittagong,Chittagong-4331,Bangladesh [3]Institute of Global Innovation Research,Tokyo University of Agriculture and Technology,3-8-1 Harumi-cho,Fuchu-shi,Tokyo 183-8538,Japan

出　　处：《Asian Pacific Journal of Tropical Medicine》2024年第12期553-562,I0008-I0012,共15页亚太热带医药杂志(英文版)

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.

摘　　要：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.

关 键 词：Dengue viruses(DENVs) DENV sero-specificity DENV serotype-cross-talks Primary DENV infections Secondary DENV infections Multivalent DENV-ED3s 

分 类 号：R51[医药卫生—内科学]