Impaired humoral and cellular response to primary COVID‐19 vaccination in patients less than 2 years after allogeneic bone marrow transplant

Abstract

Summary Allogeneic haematopoietic stem cell transplant (HSCT) recipients remain at high risk of adverse outcomes from coronavirus disease 2019 (COVID‐19) and emerging variants. The optimal prophylactic vaccine strategy for this cohort is not defined. T cell‐mediated immunity is a critical component of graft‐versus‐tumour effect and in determining vaccine immunogenicity. Using validated anti‐spike (S) immunoglobulin G (IgG) and S‐specific interferon‐gamma enzyme‐linked immunospot (IFNγ‐ELIspot) assays we analysed response to a two‐dose vaccination schedule (either BNT162b2 or ChAdOx1) in 33 HSCT recipients at ≤2 years from transplant, alongside vaccine‐matched healthy controls (HCs). After two vaccines, infection‐naïve HSCT recipients had a significantly lower rate of seroconversion compared to infection‐naïve HCs (25/32 HSCT vs. 39/39 HCs no responders) and had lower S‐specific T‐cell responses. The HSCT recipients who received BNT162b2 had a higher rate of seroconversion compared to ChAdOx1 (89% vs. 74%) and significantly higher anti‐S IgG titres (p = 0.022). S‐specific T‐cell responses were seen after one vaccine in HCs and HSCT recipients. However, two vaccines enhanced S‐specific T‐cell responses in HCs but not in the majority of HSCT recipients. These data demonstrate limited immunogenicity of two‐dose vaccination strategies in HSCT recipients, bolstering evidence of the need for additional boosters and/or alternative prophylactic measures in this group.

Specific immune response to mRNA vaccines against COVID-19 in patients receiving allogeneic stem cell transplantation for myeloid malignancy was altered by immunosuppressive therapy

“…Using an ELISPOT-IFNγ quantification of in vitro expanded T cells, our detection rate of S1- and S2- specific T cells (50% and 61% of HSCT recipients and 60% and 100% of HC, respectively) was higher than in the study of Ram et al, (6) and of Lindemann et al (7) which referred positive response in 18% and 27% of HSCT recipients, respectively. On the other hand, in other studies [9] , [10] , [11] , the detection rates of specific T- cell response in patient groups were higher (70, 78, 82%). The highest detection rate was achieved using the S1-specific T-cell derived IFNγ-release assay in whole blood where positive T cell response was detected in 90.4% of HC and 72% of HSCT recipients.…”

“…In some of the previous studies, the effects of gender [6] , [7] and type of vaccine [9] were observed in connection with antibody response but not with T cell responses. In concordance with their results, we did not find a significant association between the vaccine- specific T- cell response and age, gender, basal diagnosis or HSCT characteristics.…”

“…Their specific T cell responses to the vaccine have been analysed in only six studies so far and deficient response to SARS-CoV-2 antigens was found in all of them. Two doses of the vaccine elicited positive T cell responses against the spike protein in 19–83% of HSCT recipients [6] , [7] , [8] , [9] , [10] , [11] . The aim of our study was to determine how the reconstitution of the cellular immune system, immunosuppressive medications, and other demographic and clinical covariates influence T cell responses specific for the surface glycoprotein of SARS-CoV-2 virus (S antigen) after two doses of an mRNA vaccine against COVID-19 in patients with myeloid malignancies treated with allo-HSCT.…”

Allogeneic hematopoietic stem cell transplantation in the COVID-19 era

“…dose, associated with a larger pool of persistent memory T cells (103,104,106). Inferior results in allo-HSCT recipients as compared with a healthy control group could be explained, at least in part, by a more immature immune system with more frequent lymphopenia and the use of immunosuppressants or steroids, the same predictive factors as those reported in humoral response studies.…”

Revised Guidelines for Coronavirus Disease 19 Management in Hematopoietic Cell Transplantation and Cellular Therapy Recipients (August 2022)

“…Responses to COVID-19 vaccines are likely to be blunted in HCT or cell therapy recipients, compared with healthy individuals 6 . However, despite the scarcity of data, the high level of protection afforded to those vaccinated in the clinical trials, and the overall safety of the vaccine in clinical trials and post-emergency use authorization (EUA) experience, ASTCT and ASH strongly support vaccination of this vulnerable patient population, along with their caregivers, family members, and household contacts.…”