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

• Published in: Asian Pacific journal of tropical medicine 2024-12, Vol.17 (12), p.553-562
• Main Authors: Islam, Md. Din, Yesmin, Sanjida, Sharmin, Tahmina, Khan, Md. Ayoub, Kuroda, Yutaka, Islam, M. Monirul
• Format: Article
• Language: English
• Subjects: dengue viruses (denvs); denv sero-specificity; denv serotype-cross-talks; multivalent denv-ed3s; primary denv infections; secondary denv infections
• ISSN: 1995-7645; 2352-4146
• DOI: 10.4103/apjtm.apjtm_257_24

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.