BRIEF RESEARCH REPORT article
Front. Immunol.
Sec. Viral Immunology
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1662138
This article is part of the Research TopicImmunology of Vector-borne Tropical Diseases of the AmericasView all 4 articles
FcγRIIIA-Activating Antibodies in Dengue Virus Infection Reveals a Distinct, Transient Cross-Reactive Profile
Provisionally accepted
- 1Virology Section, Research Centre for Tropical Diseases and Faculty of Microbiology, University of Costa Rica, San José, Costa Rica
- 2Institute of Virology, University Medical Center, Faculty of Medicine, University of Freiburg; Freiburg, Germany, Freiburg, Germany
- 3University of Costa Rica, San José, Costa Rica
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Dengue viruses (DENVs), members of the Flavivirus genus, comprise four antigenically distinct serotypes (DENV-1 to DENV-4) transmitted primarily by Aedes aegypti. Clinical outcomes of DENV infection range from mild to severe, with the host antiviral immune response playing a pivotal role in disease progression. Antibody responses to DENV include serotype-specific (homotypic) and cross-reactive (heterotypic) antibodies, both of which can mediate protective immunity or contribute to immunopathogenesis through antibody-dependent enhancement (ADE). The balance between these outcomes is influenced by multiple host and viral factors. Although antibody effector mechanisms rely on Fc-gamma receptor (FcγR) interactions, these are often overlooked in the assessment of antibody function. In particular, FcγRIIIA has been implicated in both protective and pathogenic roles during viral infection. To investigate its contribution, we employed FcγRIIIA-CD3ζ reporter cells to evaluate receptor activation by polyclonal sera from individuals with acute and past DENV infections. Neutralization capacity and enhancement potential were also analyzed. The FcγRIIIA activation assay revealed a distinct humoral profile, primarily mediated by cross-reactive antibodies, which differed from neutralization and enhancement patterns. This profile increased during the post-acute phase of infection but waned within two years. These findings highlight the dynamic nature of antibody responses, where the same antibody populations may contribute to cross-protection or immunopotentiation depending on the context. Overall, this study underscores the importance of FcγR-mediated effector functions in shaping DENV immunity and pathogenesis. The FcγRIIIA activation assay provides a valuable tool to characterize functional antibody responses, informing future efforts in vaccine and therapeutic development.
Keywords: denv, humoral response, Antibody-dependent enhancement (ADE), FcγRIIIA, CD16A
Received: 08 Jul 2025; Accepted: 04 Sep 2025.
Copyright: © 2025 Soto-Garita, Murillo, Hengel and Corrales-Aguilar. 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: Eugenia Corrales-Aguilar, University of Costa Rica, San José, Costa Rica
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