Significant Production of Serum and Mucosal Anti-Spike-IgA Antibodies After Vaccine-Encoded or SARS-CoV-2-Infection-Induced Spike-Exposures in Patients with Asthma Treated with Monoclonal Antibodies Compared to Conventional Therapy

Introduction: It has been proposed that patients with asthma on monoclonal antibodies (mAb) targeting Interleukin-5 (IL-5), IL-4/IL-13 pathways or IgE may demonstrate insufficient defense against viral infections requiring strong T-helper-cell-type-1-(Th1) for neutralizing antibody production and cytotoxic CD8+ T-cell responses for efficient clearance of the viral pathogens. It is a matter of debate whether those mAb may impair the immune response against SARS-CoV-2-spike-protein by interacting with cytokines critical for B-cell differentiation and antibody maturation. This controlled cross-sectional cohort study aimed to characterize the mucosal and serum humoral immune response as well as the cellular reactivity against spike-protein in asthma patients on mAb or on conventional treatment (conv). Materials and Methods: Nasal and serum anti-spike-IgG and -IgA concentrations, avidity, neutralizing IgG and cytokine profiles were assessed using serological and neutralization assays and bead-based cytokine detection in nine patients on mAb matched to nine patients on conv who had received COVID-19-mRNA-vaccination. Proportions of spike-induced subpopulations of T- and B-cells were investigated by flow cytometry. Results: Blockade of IL-5 and IL-5 receptor showed higher serum and nasal concentrations of anti-spike-IgA against recombinant-binding-domain-(RBD) and spike-protein-1-(S1) and similar concentrations of anti-spike-IgG compared to mAb or conv therapy. A spike-specific CD8+ T-cell-driven immune response with increased cytotoxic markers was seen in anti-IL-5 treatments. Baseline Th1 responses correlated with IFNγ- and TNFα-production in supernatants of spike-protein-stimulated cultures in all patients. Conclusion: The findings indicate a significant specific adaptive immune response to SARS-CoV-2-spike-protein exposures by Th1- and Th2-driven responses with a significant response by serum and mucosal anti-S1 and anti-RBD-IgA in anti-IL-5-treated patients compared to IL-4/IL-13-targeting, anti-IgE or conventional therapies. Thus, based on the results it may be expected that immunogenicity of COVID-19-mRNA-vaccines or infection-induced spike-exposures is equivalent between asthma patients on monoclonal antibodies compared to those treated with conventional therapy.