Exposure to SARS-CoV-2 spike protein induces antigen specific IgE and basophil activation

Abstract The spike glycoprotein of SARS-CoV-2 (S) has been used as a main target antigen for vaccine design. There are concerns of vaccine-induced allergies, but mostly about allergic responses to the adjuvant. We, however, found that repetitive exposure to SARS-CoV-2 spike, not Nucleocapsid (N) protein, can induce robust type 2 inflammation in the airway of mice, which is exacerbated by the presence of house dust mite allergens. This type 2 inflammation is accompanied with elevated IgE and neutralizing antibody production. To further test whether spike glycosylation influences these responses, we compared the immunogenicity of insect cell expressed spike (in-S), mammalian cell expressed spike (m-S) and deglycosylated spike (dg-S). With intranasal treatment, in-S induced high levels of anti-spike/S1 specific IgE, while m-S and dg-S induced detectable NAb titers as determined by pseudo-virus (PV) neutralization assays. Moreover, exposure to in-S induced a significant amount of IgE+ basophils in the spleens and lungs of the mice. These spike-induced phenotypes are dependent on the TLR4/MyD88 and STAT6 signaling pathways. When delivered via intramuscular immunization following the priming/boosting protocol, spike protein induced high levels of antigen-specific IgE and IgE+ basophils. Of note, in-S induced the highest level of anti-spike/S2 IgE. However, interestingly, deglycosylation of spike antigen resulted in enhanced induction of NAbs and spike-specific CD8+ T cells following intramuscular immunization. Together, our data suggests that vaccination with SARS-CoV-2 spike may induce antigen-specific allergic response, while immunization with the deglycosylated spike protein may help enhance protective immune responses. Supported by National Institutes of Health (R01 AI151139, R56 AI146226 and P20 GM130555). W. Huang also received research support from MegaRobo Technologies Corporation.