An unexpected IgE anti-Receptor binding domain response following natural infection and different types of SARS-CoV-2 vaccines

The humoral response of SARS-CoV-2 has been studied, primarily focusing on the classical IgG and subclasses. Although IgE antibodies are typically specific to allergens or parasites, a few reports describe its production in response to SARS-CoV-2 and other viruses. Here, we investigated IgE-specific to Receptor Binding Domain (RBD) of SARS-CoV-2 in a Brazilian cohort following natural infection and vaccination. Samples from 59 volunteers were assessed after infection (COVID-19), primary immunization with vectored (ChAdOx1) or inactivated (CoronaVac) vaccines, and booster immunization with mRNA (BNT162b2) vaccine. Natural COVID-19 induced IgE, but vaccination increased its levels. Subjects vaccinated with two doses of ChAdOx1 exhibited a more robust response than those vaccinated with two doses of CoronaVac; however, after boosting with BNT162b2, all groups had similar IgE levels. IgE presented intermediate-to-high avidity, especially after the booster. We also found IgG4 antibodies, mainly after booster, and its levels presented a moderate correlation with IgE. ELISA results were confirmed by controls assays, using IgG depletion by protein G and lack of reactivity with heterologous antigen. In our cohort, no clinical data could be associated with the IgE response. We encourage studies about IgE and its role in immunity, beyond allergies and parasitic infections.