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Monomeric DENV-reactive IgA contributes protective and non-pathologic functions during DENV infection
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Waickman, Adam
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Spring 2024
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2024-01
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Dengue, caused by the 4 serotypes of dengue viruses (DENVs), is a tropical and subtropical vector-borne febrile illness which causes a significant global disease burden. A particular immunological feature contributing to severe disease is antibody-dependent enhancement (ADE), in which IgG isotype antibodies raised during a primary DENV infection opsonize and enhance the infectivity of DENVs during a secondary heterotypic infection. We and colleagues have described a monomeric serum IgA response during dengue infection. Here, we report on the functional characteristics of monomeric IgA in DENV infection. We show that isotype conversion of IgG to IgA preserves neutralization capacity while abrogating enhancing capacity. We show that DENV-specific IgA competitively antagonizes both IgG-mediated infection and downstream secretion of pro-inflammatory cytokines. This effect is largely attributable to the lower avidity of IgA-DENV immune complexes for permissive cells compared to IgG-DENV complexes. These findings have implications for serodiagnosis, therapeutics, and assessing risk of severe disease.