Deficiency of SARS-CoV-2 T-cell responses after vaccination in long-term allo-HSCT survivors translates into abated humoral immunity

Abstract

Recipients of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for hematological diseases are at risk of severe disease and death from COVID-19. To determine the safety and immunogenicity of BNT162b2 and mRNA-1273 COVID-19 vaccines, samples from 50 infection-naïve allo-HSCT recipients (median 92 months from transplantation, range 7-340 months) and 39 healthy controls were analyzed for serum IgG against the receptor-binding-domain (RBD) within spike 1 (S1) of SARS-CoV-2 (anti-RBD-S1 IgG) and for SARS-CoV-2-specific T-cell immunity, reflected by induction of T-cell-derived interferon-γ in whole blood stimulated ex vivo with fifteen 11-mer S1-spanning peptides. The rate of seroconversion was not significantly lower in allo-transplanted patients than controls with 24% (12/50) and 6% (3/50) of patients remaining seronegative after the first and second vaccination, respectively. However, 58% of transplanted patients lacked T-cell responses against S1 peptides after 1 vaccination compared with 19% of controls (OR 0.17; P=0.009, Fisher's exact test) with a similar trend after the second vaccination where 28% of patients were devoid of detectable specific T-cell immunity, compared with 6% of controls (OR 0.18, P=0.02, Fisher's exact test). Importantly, lack of T-cell reactivity to S1 peptides after vaccination heralded substandard levels (<100 BAU/ml) of anti-RBD-S1 IgG 5-6 months after the second vaccine dose (OR 8.2, P=0.007, Fisher's exact test). We conclude that while allo-HSCT recipients achieve serum anti-RBD-S1 IgG against SARS-CoV-2 after 2 vaccinations, a deficiency of SARS-CoV-2-specific T-cell immunity may subsequently translate into insufficient humoral responses. This trial is registered at EudraCT as 2021-000349-42.

Predictors of Covid-19 Vaccination Response After In-Vivo T-Cell–Depleted Stem Cell Transplantation

“… 15 , 24 , 70 Einarsdottir found deficient T-cell responses in patients with low-level serologic response. 13 But Clemenceau et al regularly found T-cell responsiveness in the absence of serologic response. 71 Others have shown that vaccine-induced SARS-Cov-2 S antibody levels in transplant patients and other patients with hematological malignancies are lower than those of healthy volunteers.…”

“…Recent reports on covid-19 vaccination in allogeneic transplant recipients have shown encouraging results. 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 But nearly all published data pertain to patients undergoing stem cell transplantation from adult donors. Conditioning regimens or graft versus host disease (GVHD) prophylaxis are usually not detailed.…”

Cellular and Humoral Immunity after the Third Vaccination against SARS-CoV-2 in Hematopoietic Stem-Cell Transplant Recipients

“…The results of the antibody ELISA and neutralization assay indicate that, after the third vaccination, antibody concentrations and the distribution of titers remained similar in immunosuppressed individuals, whereas a significant increase was seen in healthy controls. Other studies have also previously shown that the humoral immune response to SARS-CoV-2 vaccination is reduced in 30-60% of HSCT patients [13,14,23]. Currently, there are very few studies on immune responses after third vaccination in HSCT patients.…”

“…HSCT was performed at a median of 4.1 years (range 0. [5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24] prior to blood sampling. The subgroup tested prior to the third vaccination contained 10 males and 14 females; the median age was 62 years (range 39-73).…”

COVID-19 vaccine-induced adverse events predict immunogenicity among recipients of allogeneic hematopoietic stem cell transplantation

“…Recipients of allogeneic haematopoietic stem cell transplantation (allo-HCT) are at elevated risk for severe disease and death from COVID-19 1,2 and mount suboptimal immune responses following COVID-19 vaccination, in particular during the first years after transplantation [3][4][5][6][7] . Previous studies in healthy individuals support an association between adverse reactions after COVID-19 vaccination and induced humoral immunity 8,9 but whether adverse vaccine reactions also are associated with T cell reactivity remains to be elucidated.…”