The CD40-1C>T Polymorphism (rs1883832) Affects the Intensity of IgA Antibody Responses After BNT162b2 mRNA COVID-19 Vaccination

Background: The effectiveness of COVID-19 vaccination strategies is affected by several factors including the genetic background of the host. In our study we evaluated the contribution of the functional polymorphism rs1883832 affecting the Kozak sequence of the CD40 gene (c.-1C>T) to humoral immune responses after vaccination with the spike protein of SARS-CoV-2. Material and Methods: The rs1883832 polymorphism was analyzed by PCR-RFLP in 476 individuals (male/female: 216/260, median age: 55·0 years, range: 20-105), of whom 342 received the BNT162b2 mRNA vaccine and 134 adenovirus-based vector vaccines (67 on ChAdOx1-nCoV-10 vaccine, 67 on Ad.26.COV2.S vaccine). IgG and IgA responses were evaluated with chemiluminescent microparticle and ELISA assays on days 21, 42 and 90 after the first dose. Results: The T allele of the rs1883832 polymorphism (allele frequency: 32·8%) was significantly associated with lower IgA levels and represented, as revealed by multivariate analysis, an independent risk factor for reduced anti-spike protein IgA levels on days 42 and 90 following BNT162b2 mRNA vaccination. Similar to serum anti-spike IgA levels, lower anti-spike IgA concentrations in saliva and reduced CD40 expression on the surface of circulating B cells correlated with the T allele of rs1883832. Finally, the intensity of IgA and IgG responses on day 42 significantly affected the prevalence of COVID-19 after vaccination. Conclusion The rs1883832 polymorphism may be used as a molecular predictor of the intensity of anti-spike IgA responses after BNT162b2 mRNA vaccination.Funding: The study was funded by own resources of the Department of Immunology & Histocompatibility and the Laboratory of Hygiene and Epidemiology of Faculty of Medicine,University of Thessaly, Greece.Declaration of Interest: All authors declare no conflicts of interest related to this study.Ethical Approval: The study was conducted according to the principles of the Helsinki Declaration and was approved by the ethical committee of the Faculty of Medicine, University of Thessaly (No. 2116, 22 April 2020).