Cellular and Humoral SARS-CoV-2 Vaccination Responses in 192 Adult Recipients of Allogeneic Hematopoietic Cell Transplantation

Abstract

To determine factors influencing the vaccination response against SARS-CoV-2 is of importance in recipients of allogeneic hematopoietic cell transplantation (allo-HCT) as they display an increased mortality after SARS-CoV-2 infection, an increased risk of extended viral persistence and reduced vaccination response. Real-life data on anti-SARS-CoV-2-S1-IgG titers (n = 192) and IFN-γ release (n = 110) of allo-HCT recipients were obtained using commercially available, validated assays after vaccination with either mRNA (Comirnaty™, Pfizer-BioNTech™, NY, US and Mainz, Germany or Spikevax™, Moderna™, Cambridge, Massachusetts, US) or vector-based vaccines (Vaxzevria™,AstraZeneca™, Cambridge, UK or Janssen COVID-19 vaccine™Johnson/Johnson, New Brunswick, New Jersey, US), or after a heterologous protocol (vector/mRNA). Humoral response (78% response rate) was influenced by age, time after transplantation, the usage of antithymocyte globulin (ATG) and ongoing immunosuppression, specifically corticosteroids. High counts of B cells during the vaccination period correlated with a humoral response. Only half (55%) of participants showed a cellular vaccination response. It depended on age, time after transplantation, ongoing immunosuppression with ciclosporin A, chronic graft-versus-host disease (cGvHD) and vaccination type, with vector-based protocols favoring a response. Cellular response failure correlated with a higher CD8+ count and activated/HLA-DR+ T cells one year after transplantation. Our data provide the basis to assess both humoral and cellular responses after SARS-CoV2 vaccination in daily practice, thereby opening up the possibility to identify patients at risk.

Keywords: IFN-γ release assay (IGRA); SARS-CoV-2; allogeneic hematopoietic cell transplantation (allo-HCT); specific antibody titer.

Figure 1

Humoral and cellular SARS-CoV-2 vaccination response. (A) Box plots display age at allo-HCT and the time from allo-HCT to best measured humoral (A) and cellular response (C) stratified according to responders and nonresponders. Points represent individual patients. (B,D) In the left column, pie charts show frequencies of usage of antithymocyte globulin (ATG), active ongoing treatment with immunosuppressants (ISP) and the usage of specific immunosuppressive agents in responders versus nonresponders. The right column displays frequencies of donor type, intensity of the conditioning chemotherapy and the vaccination protocol used in responders and nonresponders. Matched unrelated donors (MUD), matched related donors (MRD), mismatched unrelated donors (MMUD), mismatched related donors (MMRD), HLA-haploidentical donors (HAPLO), myeloablative conditioning (MAC), reduced toxicity myeloablative conditioning (RTC) and reduced intensity conditioning (RIC). Vaccination protocols displayed are based on only messenger RNA (mRNA) vaccines, only viral vector vaccines (V) or a heterologous combination of one-time viral vector vaccine followed by an mRNA vaccine (V + mRNA). *, p < 0.05.