Patterns of spike-specific IgG subclasses after different types of COVID-19 vaccines in patients with hereditary angioedema due to C1 inhibitor deficiency.

Objectives: Different forms of vaccines have been introduced to reduce hospitalizations and prevent the risk of serious coronavirus disease 2019 (COVID-19). Monitoring of the SARS-CoV-2 spike-specific IgG subclasses after COVID-19 vaccinations will provide additional details about specific long-term immune memory in patients with hereditary angioedema due to C1 inhibitor deficiency (HAE-C1INH). Methods: We examined four HAE-C1INH patients vaccinated with primary vector (Sputnik), mRNA-based (Pfizer-BioNTech), or inactivated (Sinopharm) vaccines and one booster mRNA-based vaccine in the Hungarian Angioedema Centre of Reference and Excellence. The levels of each spike-specific IgG subclass and the total spike-specific IgG were determined by in-house ELISA. Total serum IgG and IgG subclasses were measured by nephelometry. Results: Patient 1 who was infected after mRNA-based vaccination had high spike-specific IgG4 to total spike-specific IgG ratio (41 %). Two patients who had vector-based vaccination without infection and the patient with inactivated vaccination had low spike-specific IgG4 to total spike-specific IgG ratios. The patient with slightly higher total serum IgG4 has also had high total serum IgG4 before the COVID-19 pandemic. Conclusion: Taken together, our study was an individual-level observation, where spike-specific IgG4 antibody response appeared several months after mRNA-based SARS-CoV-2 immunization in a HAE-C1INH type I patient. Further investigations are planned to examine the in vitro complement activation of spike-specific IgG4 after mRNA-based vaccinations.