1970. SARS-CoV-2 T-cell specific responses in allogeneic hematopoietic stem cell transplant recipients after second and third dose of BNT162b2 mRNA vaccine

Abstract

Background Cell-mediated immunity (CMI) after anti-Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV)-2 vaccines has been poorly explored in recipients of allogeneic hematopoietic stem-cell transplantation (HSCT), especially with regard to the 3rd dose (booster). Aim of the study was to assess the specific T-cell responses before and after the 3rd dose of BNT162b2 mRNA vaccine in a cohort of allogeneic HSCT recipients, and compare it with healthy donors (HD). Methods Allogenic HSCT recipients and HD were enrolled before receiving the 3rd dose of BNT162b2 mRNA vaccine. Whole blood for T-cell specific responses was collected before (T1) and 8 weeks after (T2) the booster administration. T-cell responses were assessed with an Interferon (IFN)-γ release assay (IGRA), after overnight stimulation of heparin whole blood with pools of lyophilized peptides, covering the immunodominant sequence of the Spike (S) protein. IFN-γ production was assessed with an enzyme linked immunosorbent assay (ELISA). Statistical analysis was performed with GraphPadPrism. Results 14 HSCT recipients (8M, 6F) and 15 HD (7M, 8F) were enrolled (table 1). Median age was 47 [39-59] and 41 [31-48] years in the HSCT and HD groups, respectively. Time between the vaccine 2nd dose and T1 was significantly longer in HD than HSCT recipients (p< .001), while the time between T1 and T2 did not differ between the two groups. SARS-CoV-2 S specific T-cell responses at T1 were inferior in HSCT recipients compared to HD (median IFN-γ production: 463 vs 231 ng/ml, respectively), although the difference did not reach the statistical significance. No differences were observed at T2. In a before-after analysis, SARS-CoV-2 S specific T-cell responses were significantly increased in HSCT recipients at T2 compared to T1 (median IFN-γ production: 267 vs 881 ng/ml, p=0.02) (Figure 1). At T1, 3 HSCT recipients showed very low or no IFN-γ production, while at T2 only 1 patient still had undetectable IFN-γ production after S peptide stimulation. Table 1:Clinical characteristics of allo-HSCT recipients and HDHSCT: hematopoietic stem-cell transplantation; IQR: interquartile range; ALL: acute lymphoblastic leukemia; AML: acute myeloid leukemia; MDS: myelodysplastic syndrome; T-ALL: T-cell acute lymphoblastic leukemia; AA: aplastic anemia; PMF: primary myelofibrosis; MUD: matched unrelated donor; MMUD: mismatched unrelated donors; NA: not applicable; ns: not significant.Figure 1:IFN-γ Production after Spike peptide stimulation of whole blood from allogenic HSCT recipients and HD.Comparison of IFN-γ production after Spike peptide stimulation of whole blood in allogenic HSCT recipients and HD at T1 (1.A) and T2 (1.B) (before and after BNT162b2 mRNA vaccine 3rd dose, respectively). Before-after representation of IFN-γ production after Spike peptide stimulation in HD and allogenic HSCT recipients (1.C). Conclusion SARS-CoV-2 IGRA represents a useful tool to assess CMI, also in immunocompromised hosts. An additional 3rd BNT162b2 mRNA vaccine booster dose seems to enhance CMI in allogenic HSCT recipients. Further studies are needed to evaluate the duration of SARS-CoV-2 CMI in HSCT recipients compared to HD. Disclosures All Authors: No reported disclosures.

Immunologic responses to the third and fourth doses of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines in cell therapy recipients: a systematic review and meta-analysis

“…Six studies evaluated the cellular immune response to a third vaccine dose, focusing on interferon-gamma (IFNγ) production by CD4+ and CD8+ T-lymphocytes. Additional assessments included IL-2 release, CD154 upregulation, and tumor necrosis factor alpha (TNF-α) production [29,[33][34][35][36][37]. Albiol et al 's study [33] found that 76.6% of patients vaccinated within three to 24 months (G1) and 94.4% vaccinated after 24 months (G2) from HSCT had a positive response, with no significant statistical difference.…”

“…Another study by Ram et al [29] reported that 83% of CAR-T patients (5/6) and 100% of allo-HSCT patients (10/10) showed a positive cellular response post-third-dose injection. Furthermore, Marco et al [36] demonstrated a significant augmentation in the SARS-CoV-2 S specific T-cell responses among HSCT recipients after third dose by performing a before-after analysis.…”