Mrna-1273 sars-cov-2 vaccine in recently transplanted allogeneic hematopoietic cell transplant recipients: cellular and humoral immune responses and booster effect

Topic: 30. Infections in hematology (incl. supportive care/therapy) Background: Allogeneic hematopoietic stem cell transplant (HCT) recipients are at high risk of severe COVID-19 despite vaccination. Few studies have analyzed cellular responses and booster dose results, especially in the early period after HCT. Aims: The main objective was to describe and compare both IgG and T-cell responses to SARS-CoV-2 vaccination in recently transplanted patients (RTP) versus two other groups: long-term transplanted patients (LTTP) and healthy controls. Methods: This single-center, prospective, and observational study recruited all consecutive adult allo-HCT recipients who were between 3 and 24 months from the infusion date in March-April 2021 (RTP, n=49). Another cohort of relapse-free-GVHD and immunosuppression-free long-term (>2 years from HCT date) transplanted patients was included (LTTP, n= 19). All patients received the mRNA-1273 (Spikevax®) vaccine (two doses 28 days apart and a third dose after 6 months). In addition, a control group of 20 healthy volunteers who received the first 2 doses was recruited. The humoral response was assessed through in-house ELISAs for IgG antibodies against the SARS-CoV-2 S1 protein. The cellular response was evaluated using a commercial interferon-gamma release assay method (QuantiFERON SARS-CoV-2). Determinations were made one and three months after the second dose (T1 and T2, respectively), and one month after the third dose (T3). Results: Median age was 56 years (26-73) for RTPs and 60 (25-70) for LTTPs (no matching was attempted). Most patients received post-transplant cyclophosphamide plus tacrolimus as GVHD prophylaxis (69.4%/57.9% RTPs/LTTPs). At T1, RTPs showed lower IgG antibody titers than both LTTP (mean 0.50 vs 0.66 arbitrary units -AU-, p=0.01) and healthy controls (0.94 AU, p<0.0001). At T2 no differences were seen between both transplant groups (0.37 vs 0.40 AU, p=0.55), while controls presented higher titers (0.79 AU, p<0.0001). Responses at T3 were similar between RTPs and LTTPs (0.54 vs 0.56 AU, p=0.82) [Fig. 1A-D]. The rate of positive T-cell responses was lower in RTPs than in controls at both T1 and T2 (61.2% vs 95%, p=0.007; 59.2% vs 100%, p=0.001, respectively). Contrarily, differences in cellular responses were not statistically significant at any timepoint either between RTPs and LTTPs [61.2% vs 78.9%, p=0.25 (T1); 59.2% vs 84.2%, p=0.08 (T2); 76.6% vs 94.4%, p=0.15 (T3)] or between LTTPs and healthy controls [78.9% vs 95%, p=0.18 (T1); and 84.2% vs 100%, p=0.23 (T2)]. Interestingly, there were no declines in the T-cell immune response between T1 and T2 in any group (p=1.00), in contrast to humoral responses (Fig. 1C-E). A significant number of patients exhibited dissociated responses (only cellular or humoral), especially amongst RTPs (Fig. 1F-H). The booster increased positive responses in RTPs. Nineteen out of the 33 (58%) RTPs with a negative humoral response at T2 turned positive after the booster (35.4% of increase, p<0.001). As for the cellular response, nine out of 20 (47%) negative RTPs at T2 turned positive at T3 (18% of increase, p<0.05). A multivariable logistic regression revealed ongoing immunosuppressive treatment as the main factor undermining both humoral and cellular response (especially after the booster). Others less relevant were low total IgG and low B-cell counts. Summary/Conclusion: Recently transplanted allo-HCT patients show an impaired SARS-CoV-2 vaccine response compared to healthy controls, but also compared to long-term transplanted patients. A booster dose increases the likeliness of achieving a positive response, both for humoral and cellular immunity, despite being less efficacious in those with active immunosuppressive treatment.Keywords: Allogeneic hematopoietic stem cell transplant, COVID-19, Cellular immunity