Variances in Humoral Responses to Different Spike Protein Domains After SARS-CoV-2 Vaccination in Lung and Heart Transplant Recipients

PURPOSE: Solid organ transplant recipients are lacking an adequate immune response to SARS-CoV-2 vaccination. Therefore, these patients are still at risk and potentially in need of booster vaccinations. Furthermore, it is important to differentiate between the recipients of distinct organs. The efficacy of SARS-CoV-2 vaccination is usually examined via antibodies specific for the spike protein with assays containing the S1 and receptor-binding-domains (RBD) and rather rarely the S2 domain. To gain information about the humoral response in Tx recipients, it is feasible to compare the immunogenicity of these three domains. To address this, we compared the IgG antibody levels specific for the three spike protein domains in heart (HTx) vs lung (LTx) transplant recipients. METHODS: Blood plasma 4-6 weeks after the second dose of SARS-CoV-2 vaccination (85% mRNA) of n=100 LTx and n=40 HTx patients was analysed for S1, S2 and RBD-specific IgG antibodies by Luminex-based multiplex assays. The threshold for positive antibody responses was set separately for each spike domain based on the median MFI + 2σ in an unexposed pre-pandemic control group. RESULTS: For all three spike protein domains, HTx patients showed a significantly higher rate of positive IgG responses than the LTx patients (73% vs 43%). The comparison of MFI values for S1-, S2- and RBD-specific IgG further underlines the superior antibody response by HTx patients with higher MFI values for S1 (p = 0.0001, S2 p = 0.008, RBD p < 0.0001). In the LTx cohort, MFI values for S2- (p < 0.0001) as well as for RBD-specific IgG (p < 0.0001) were higher than for S1. The same applies for S2 vs S1 (p < 0.0001) and RBD vs S1 (p = 0.0018) in the HTx cohort. Comparing the MFI of S2 vs RBD, the levels of domain-specific IgG were higher for S2 than RBD in both LTx (p < 0.0001) and HTx patients (p = 0.0914). CONCLUSION: HTx patients exhibit a moderately good IgG response to vaccination while LTx recipients show lower antibody responses. Based on the more efficient antibody production against S2 as opposed to the RBD and especially S1-domain, the S2-specific IgG response should be taken into consideration when evaluating the general immune response and the resulting protection after SARS-CoV-2 vaccination in transplant recipients. Both groups of patients might benefit from booster vaccinations.