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.