B Cell Aplasia Is the Most Powerful Predictive Marker for Poor Humoral Response after BNT162b2 mRNA SARS-CoV-2 Vaccination in Recipients of Allogeneic Hematopoietic Stem Cell Transplantation

Jullien, Maxime; Bourgeois, Amandine Le; Coste‐Burel, Marianne; Péterlin, Pierre; Garnier, Alice; Rimbert, Marie; Imbert, Berthe‐Marie; Gouill, Steven Le; Moreau, Philippe; Mahé, Béatrice; Dubruille, Viviane; Blin, Nicolas; Lok, Anne; Touzeau, Cyrille; Gastinne, Thomas; Tessoulin, Benoît; Vantyghem, Sophie; Béné, Marie C.; Guillaume, Thierry; Chevallier, Patrice

doi:10.1016/j.jtct.2022.02.018

Cited by 10 publications

(11 citation statements)

References 13 publications

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“…Factors associated with the absence of humoral responses have been also well described in the setting of allotransplant including low B lymphocytes count, time-interval from allotransplant <12 months, ongoing immunosuppressive treatments and male gender [ 19 , 20 , 28 , 29 ]. Regarding factors predicting cellular response, Lindemann et al [ 20 ] demonstrated an impact of age and of the time point after transplantation and vaccination.…”

Section: Discussionmentioning

confidence: 99%

SARS-CoV-2 T-Cell Responses in Allogeneic Hematopoietic Stem Cell Recipients following Two Doses of BNT162b2 mRNA Vaccine

et al. 2022

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Background: At variance to humoral responses, cellular immunity after anti-SARS-CoV-2 vaccines has been poorly explored in recipients of allogeneic hematopoietic stem-cell transplantation (Allo-HSCT), especially within the first post-transplant years where immunosuppression is more profound and harmful. Methods: SARS-CoV-2 Spike protein-specific T-cell responses were explored after two doses of BNT162b2 mRNA vaccine in 45 Allo-HSCT recipients with a median time from transplant of less than 2 years by using INF-γ ELISPOT assay and flow-cytometry enumeration of CD4+ and CD8+ T lymphocytes with intracellular cytokine production of IFN-γ and TNF-α. Results: A strong TNF-α+ response from SARS-CoV-2-specific CD4+ T-cells was detected in a majority of humoral responders (89%) as well as in a consistent population of non-humoral responders (40%). Conclusions: T-cells are likely to participate in protection against COVID-19 viral infection, even in the absence of detectable antibody response, especially in the first years post-transplant in Allo-HSCT recipients.

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Section: Discussionmentioning

confidence: 99%

SARS-CoV-2 T-Cell Responses in Allogeneic Hematopoietic Stem Cell Recipients following Two Doses of BNT162b2 mRNA Vaccine

et al. 2022

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“…Therefore, broadening the coverage of T cell epitopes by using multiantigen vaccines may raise the long-term threshold of protection conferred by T cell immunity beyond the observed 30-50% afforded by vaccines expressing S alone, potentially maintaining protective immunity in the face of waning or reduced cross-reactive neutralizing responses as a result of the continuous emergence of new VOC. Broadly functional vaccine-elicited T cell responses could be particularly important to protect against severe disease in the immunocompromised population, such as transplant recipients, in which mounting of an effective antibody response is impaired owing to B cell aplasia (Jullien et al, 2022). Phase 2 clinical trials are underway testing the use of COH04S1 as a booster vaccine in volunteers previously vaccinated with authorized COVID-19 vaccines (NCT04639466) and COH04S1 as a primary vaccination in patients with hematopoietic cancer following bone marrow transplant or cellular therapy (NCT04977024).…”

Section: Discussionmentioning

confidence: 99%

Vaccine-induced spike- and nucleocapsid-specific cellular responses maintain potent cross-reactivity to SARS-CoV-2 Delta and Omicron variants

Chiuppesi¹,

Zaia

Faircloth³

et al. 2022

iScience

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“…Multiple studies investigated lymphopenia, which may be a surrogate marker of immune system capacity, and consider it a major pejorative factor in humoral response, often at the threshold of <1 Giga/L. If lymphocytes are studied separately as B cells, T cells, and gamma-globulinemia representing plasma cell activity, many studies report an independent impact of the B cell population only (74,80,81). One of these studies (80) goes as far as to report B cell aplasia as the strongest predictor of a poor humoral response, with a seroconversion in 9.1% in B cell aplasia group versus 95.9% in the control group.…”

Section: In Hsct Patientsmentioning

confidence: 99%

“…If lymphocytes are studied separately as B cells, T cells, and gamma-globulinemia representing plasma cell activity, many studies report an independent impact of the B cell population only (74,80,81). One of these studies (80) goes as far as to report B cell aplasia as the strongest predictor of a poor humoral response, with a seroconversion in 9.1% in B cell aplasia group versus 95.9% in the control group.…”

Section: In Hsct Patientsmentioning

confidence: 99%

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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B Cell Aplasia Is the Most Powerful Predictive Marker for Poor Humoral Response after BNT162b2 mRNA SARS-CoV-2 Vaccination in Recipients of Allogeneic Hematopoietic Stem Cell Transplantation

Cited by 10 publications

References 13 publications

SARS-CoV-2 T-Cell Responses in Allogeneic Hematopoietic Stem Cell Recipients following Two Doses of BNT162b2 mRNA Vaccine

SARS-CoV-2 T-Cell Responses in Allogeneic Hematopoietic Stem Cell Recipients following Two Doses of BNT162b2 mRNA Vaccine

Vaccine-induced spike- and nucleocapsid-specific cellular responses maintain potent cross-reactivity to SARS-CoV-2 Delta and Omicron variants

Allogeneic hematopoietic stem cell transplantation in the COVID-19 era

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