(348) Longitudinal Dynamics of SARS-CoV-2 Spike-Specific Antibody Responses in Patients on Waiting List and after Lung Transplantation

PURPOSE: Patients with end-stage lung diseases on the MHH waiting list for lung transplantation (LTx) have been vaccinated against the SARS-CoV-2 spike protein with usually three doses of the mRNA vaccine. Hence, they are supposed to develop robust antibody and T cell responses when immunized prior to LTx without the influence of immunosuppression. Therefore, we hypothesized the induction of high spike-specific IgG levels and protection against SARS-CoV-2 infection and severe COVID-19. To proof this, we aimed to analyze the IgG levels specific for the spike S1-, RBD- and S2-domains in patients on a waiting list (WL-LTx) longitudinally before and after their transplantation. METHODS: Plasma obtained pre (n=70) and post LTx (n=28) of WL-LTx patients was analyzed for spike-specific IgG by Luminex-based multiplex assays. The threshold for positivity was set separately for each spike domain based on the median MFI +2σ in a healthy, unexposed pre-pandemic control group. Patients with previous SARS-CoV-2-infection were excluded. RESULTS: 95.7% of WL-LTx patients had seroconverted for either RBD-, S1- or S2-specific IgG pre LTx and still 92.86% were positive post LTx. Overall, S1-, S2- and RBD-specific IgG MFI values did not significantly differ between pre vs. post LTx. A subanalysis of matched plasma samples (n=25) revealed that 52% of the WL-LTx patients showed a higher IgG response pre than post LTx for all three spike protein domains and 28% showed even elevated antibody levels post LTx. Interestingly, S2-specific IgG MFI values were significantly elevated compared to RBD-specific IgG MFI values, both pre (S2 vs. RBD p<0.0001) and post LTx (S2 vs. RBD p=0.0225). CONCLUSION: The majority of WL-LTx patients mounted high SARS-CoV-2 spike-specific IgG responses following vaccination pre LTx. Based on the more efficient antibody production against the S2-domain compared to RBD- and S1-domains, S2-specific IgG responses should be included also in the general evaluation of humoral immune responses to SARS-CoV-2. As expected, WL-LTx patients showed a superior antibody response to vaccination compared to LTx-recipients vaccinated only after LTx, which could even be maintained after LTx in some patients. Therefore, both patients on waiting list and LTx recipients may benefit from additional booster vaccinations after LTx.