COVID-19 Vaccination Induces Cross-Reactive Dengue Antibodies with Altered Isotype Profiles and In Vitro ADE

Dengue virus is a mosquito transmitted flavivirus that cause inapparent or mild disease but can also cause severe hemorrhagic fever in humans. Cross-reactive IgG antibodies can cause under specific conditions antibody dependent enhancement (ADE) of the infection via Fc-receptor interaction. Antibodies from SARS-CoV-2 (anti-S) causing COVID-19 disease can also cross-react against the dengue envelope (anti-E). We therefore investigated the antibody profile of these cross-reactive antibodies and their ability to induce ADE. We found that the cross-reactive anti-E in COVID-19 vaccinated are dominated by IgM/A while, anti-S from vaccinated or anti-E from dengue infected patients have an IgG1 dominated antibody profile. The low-level anti-E IgG from COVID-19 vaccinated are dominated by low Fc-affinity IgG2/4 subclass. These antibodies were able to induce in vitro ADE stronger than from Dengue infected for the 1 ^st ,2 ^nd dose of the vaccine or later omicron variant booster. This could partially be explained that ADE was inhibited by the complement system in dengue infected but not in COVID-19 vaccinated.