SARS‐CoV‐2‐specific T cells are generated in less than half of allogeneic HSCT recipients failing to seroconvert after COVID‐19 vaccination

Jarisch, Andrea; Wiercinska, Eliza; Daqiq-Mirdad, Shabnam; Hellstern, Helen; Ajib, Salem; Cremer, Anjali; Nguyen, Ngoc Thien Thu; Dukat, Alexandra; Ullrich, Evelyn; Ciesek, Sandra; Chow, Kai-Uwe; Seifried, Erhard; Bader, Peter; Bönig, Halvard; Bug, Gesine

doi:10.1002/eji.202149771

Cited by 11 publications

(8 citation statements)

References 9 publications

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“…Vaccine efficacy in HSCT recipients: While highly immunogenic in the populations included in the large-scale studies that led to vaccine licensing, at least against the original outbreak strain of SARS-CoV-2, numerous, mostly single-center immunogenicity studies have demonstrated decreased, but highly variable, in vitro immune response in HSCT recipients to a 2- or 3-dose mRNA vaccine series as measured by neutralizing antibody and/or T-cell response [ 12 , [62] , [63] , [64] , [65] , [66] , [67] , [68] , [69] , [70] , [71] ]. Not surprisingly, recency of HSCT, immunosuppressive therapy, lymphopenia, active malignancy and GVHD have all been demonstrated to be associated with dampened immune response.…”

Section: Vaccination In Hsct Recipientsmentioning

confidence: 99%

COVID-19 and HSCT (Hematopoietic stem cell transplant)

Strasfeld¹

2022

Best Practice & Research Clinical Haematology

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Section: Vaccination In Hsct Recipientsmentioning

confidence: 99%

COVID-19 and HSCT (Hematopoietic stem cell transplant)

Strasfeld¹

2022

Best Practice & Research Clinical Haematology

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“…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.…”

Section: Cellular Responsementioning

confidence: 89%

Allogeneic hematopoietic stem cell transplantation in the COVID-19 era

Bordat

Maury²,

Leclerc³

2023

Front. Immunol.

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Allogeneic hematopoietic stem-cell transplantation (allo-HSCT) recipients are especially vulnerable to coronavirus disease 19 (COVID-19), because of their profound immunodeficiency. Indeed, the first pandemic wave was marked by a high mortality rate in this population. Factors increasing immunodepression such as older age, immunosuppressive treatments or a short delay between transplant and infection appear to worsen the prognosis. Many changes in clinical practice had to be implemented in order to limit this risk, including postponing of transplant for non-malignant diseases, preference for local rather than international donations and for peripheral blood as stem cell source, and the widespread use of cryopreservation. The great revolution in the COVID-19 pandemic came from the development of mRNA vaccines that have shown to be able to prevent severe forms of the disease. More than 75% of allo-HSCT recipients develop seroconversion after 2 doses of vaccine. Multiple studies have identified lymphopenia, exposure to immunosuppressive or anti-CD20 therapies, and a short post-transplant period as factors associated with a poor response to vaccination. The use of repeated injections of the vaccine, including a third dose, not only improves the seroconversion rate but also intensifies the immune response, both in B cells and T cells. Vaccines are an effective and well-tolerated method in this high-risk population. Some studies investigated the possibility of immune protection being transferred from a vaccinated donor to a recipient, with encouraging initial results. However, dynamic mutations and immune escape of the virus can lead to breakthrough infections with new variants in vaccinated individuals and still represent a threat of severe disease in allo-HSCT recipients. New challenges include the need to adapt vaccine protection to emerging variants.

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“…Currently, there are very few studies on immune responses after third vaccination in HSCT patients. Most studies focus on the humoral immune response, but point to the important role of cellular immunity, which we investigated [24][25][26]. Einarsdottir et al were the only investigators of the cellular immune response.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2022

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Protecting vulnerable groups from severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) infection is mandatory. Immune responses after a third vaccination against SARS-CoV-2 are insufficiently studied in patients after hematopoietic stem-cell transplantation (HSCT). We analyzed immune responses before and after a third vaccination in HSCT patients and healthy controls. Cellular immunity was assessed using interferon-gamma (IFN-γ) and interleukin-2 (IL-2) ELISpots. Furthermore, this is the first report on neutralizing antibodies against 11 variants of SARS-CoV-2, analyzed by competitive fluorescence assay. Humoral immunity was also measured by neutralization tests assessing cytopathic effects and by ELISA. Neither HSCT patients nor healthy controls displayed significantly higher SARS-CoV-2-specific IFN-γ or IL-2 responses after the third vaccination. However, after the third vaccination, cellular responses were 2.6-fold higher for IFN-γ and 3.2-fold higher for IL-2 in healthy subjects compared with HSCT patients. After the third vaccination, neutralizing antibodies were significantly higher (p < 0.01) in healthy controls, but not in HSCT patients. Healthy controls vs. HSCT patients had 1.5-fold higher concentrations of neutralizing antibodies against variants and 1.2-fold higher antibody concentrations against wildtype. However, half of the HSCT patients exhibited neutralizing antibodies to variants of SARS-CoV-2, which increased only slightly after a third vaccination.

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SARS‐CoV‐2‐specific T cells are generated in less than half of allogeneic HSCT recipients failing to seroconvert after COVID‐19 vaccination

Cited by 11 publications

References 9 publications

COVID-19 and HSCT (Hematopoietic stem cell transplant)

COVID-19 and HSCT (Hematopoietic stem cell transplant)

Allogeneic hematopoietic stem cell transplantation in the COVID-19 era

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

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