ORIGINAL RESEARCH article
Front. Immunol.
Sec. Viral Immunology
COVID-19 Vaccination Induces Cross-Reactive Dengue Virus Antibodies with Altered Isotype Profiles and In Vitro Antibody-Dependent Enhancement
Provisionally accepted
Sebastian Reinig1
Chin Kuo1
Sheng-Yu Huang1Kuei-Ching Hsiung1,2Po-Kai Chen3
Etsuro Ito3,4
Ing-Kit Lee1,5Ching-Yen Tsai6
SHU-MIN LIN1
Shin-Ru Shih1,2*- 1Chang Gung University, Taoyuan, Taiwan
- 2Academia Sinica Biomedical Translation Research Center, Taipei City, Taiwan
- 3Waseda Daigaku, Shinjuku, Japan
- 4Kaohsiung Medical University, Kaohsiung, Taiwan
- 5Kaohsiung Chang Gung Memorial Hospital, Niaosong District, Taiwan
- 6Kaohsiung Municipal United Hospital, Kaohsiung, Taiwan
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Dengue virus is a mosquito-transmitted Flavivirus that causes inapparent or mild disease but can also cause severe hemorrhagic fever in humans. Cross-reactive IgG antibodies can cause antibody-dependent enhancement (ADE) of infection via Fc-receptor binding under specific conditions. Antibodies against the spike protein (anti-S) of SARS-CoV-2, the cause of COVID-19, can also cross-react with the dengue virus envelope protein (anti-E). We therefore investigated the antibody profiles of these cross-reactive antibodies from COVID-19 vaccinated (mRNA, Adenovector, protein subunit) and Dengue recovered and their ability to induce ADE. The antibody profile of cross-reactive anti-E in COVID-19-vaccinated individuals was dominated by IgM/A, while those for anti-S from vaccinated individuals and anti-E from dengue virus-infected patients were dominated by IgG1. Anti-E IgG, detected at low levels in COVID-19-vaccinated individuals, was dominated by the low Fc-affinity IgG2/4 subclass. These antibodies induced a stronger in vitro IgG dependent ADE than that for Dengue virus infection for the 1st and 2nd dose of the vaccine or later Omicron variant booster. This phenomenon can be partially explained by the complement system's role in inhibiting ADE in dengue-infected but not in COVID-19-vaccinated individuals.
Keywords: Dengue, isotype, Cross-reactive, Antibody-Dependent Enhancement, COVID-19
Received: 10 Aug 2025; Accepted: 13 Nov 2025.
Copyright: © 2025 Reinig, Kuo, Huang, Hsiung, Chen, Ito, Lee, Tsai, LIN and Shih. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Shin-Ru Shih, srshih@mail.cgu.edu.tw
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