ABSTRACT
Introduction: Prevention of COVID by vaccination is important in allogeneic HSCT recipients but impaired humoral and cellular responses have been reported. To gain further insights into the immune defects leading to impaired immune, we performed a high-throughput T cell receptor (TCR) repertoire profiling of cells recovered from allogeneic HSCT recipients or healthy controls after SARS-CoV2 natural infection or mRNA-based vaccination. Method(s): Peripheral blood samples were obtained from allogeneic HSCT recipients after a median of 3 months after COVID- 19 infection (n = 11) or 44 days after vaccination with 3 doses of mRNA-based SARS-CoV-2 vaccines (n = 13). Healthy controls at 1 to 3 months after SARS-CoV-2 infection (n = 10) or vaccination served as controls (n = 10). SARS-CoV-2- specific T cell clonotypes were identified by genomic DNA T-cell receptor (TCR) sequencing (immunoSEQ T-MAPTM COVID, Adaptive). SARS-CoV-2-specific T cell responses were quantified based on IFN-gamma release against a range of peptides from the SARS-CoV-2 proteins using an ELISpot assay. Result(s): HSCT recipients displayed significantly reduced SARS-CoV-2-specific T cell clonotypes compared with HC (p = 0.0037;Figure 1 A-B)as well as a less diverse TCR repertoire as revealed by higher Simpson clonality (p = 0.0079). We also observed significantly lower numbers of IFN-gamma spot forming units after stimulation of PBMCs from HSCT recipients with peptides from both the S protein (p = 0.0068) and the M plus N proteins (p = 0.0067) compared with HC. Performing the same analysis after SARS-CoV-2 mRNA vaccination, we observed a significant reduction in S-protein-specific T cell clonotypes in allogeneic HSCT recipient compared to HC (p = 0.0003;Figure 1D-E). We detected a significantly negative correlation between the Simpson clonality and the number of different S-protein specific T cell clonotypes after vaccination (r2 = 0.55, p = 7.8e-05;Figure 1F). ELISpot analysis of PBMCs recovered after vaccination and stimulated with S-protein peptides revealed significantly lower numbers of IFN-gamma spot forming units in HSCT recipients compared with HC (p = 0.019), confirming the results obtained by TCR-seq. Conclusion(s): Allogeneic HSCT recipients display a quantitative and qualitative defect in cellular SARS-CoV-2-specific responses asscociated with a reduced TCR repertoire after COVID-19 infection and vaccination. (Figure Presented).