Safety and Immunogenicity After a Three-Dose SARS-CoV-2 Vaccine Schedule in Allogeneic Stem Cell Transplant Recipients

• Published in: Transplantation and cellular therapy Vol. 28; no. 10; pp. 706.e1 - 706.e10
• Main Authors: Kimura, Muneyoshi, Ferreira, Victor H., Kothari, Sagar, Pasic, Ivan, Mattsson, Jonas I., Kulasingam, Vathany, Humar, Atul, Mah, Allison, Delisle, Jean-Sébastien, Ierullo, Matthew, Majchrzak-Kita, Beata, Kumar, Deepali, Hosseini-Moghaddam, Seyed M.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.10.2022; Published by Elsevier Inc. on behalf of The American Society for Transplantation and Cellular Therapy
• Subjects: CD4-Positive T-Lymphocytes; CD8-Positive T-Lymphocytes; COVID-19 - prevention & control; COVID-19 Vaccines; Graft vs Host Disease - epidemiology; Hematopoietic Stem Cell Transplantation; Humans; Immunity, Cellular; Immunity, Humoral; Immunization, Secondary; Immunogenicity, Vaccine; Interleukin-2; Prospective Studies; SARS-CoV-2; Vaccines; SARS-CoV-2; Hematopoietic stem cell transplantation; Vaccines
• ISSN: 2666-6367; 2666-6375; 2666-6367
• DOI: 10.1016/j.jtct.2022.07.024

In allogeneic stem cell transplant (Allo-SCT) recipients, the cell-mediated and humoral immunogenicity of the 3-dose SARS-CoV-2 vaccination schedule has not been investigated in prospective studies. In a prospective cohort, we recruited 122 Allo-SCT recipients since August 2021, when Ontario began offering a 3-dose vaccine schedule for Allo-SCT recipients. We determined humoral and cell-mediated immunity and adverse effects of the 3-dose SARS-COV-2 vaccination schedule in Allo-SCT recipients. In immunogenicity analysis (n = 95), the median (interquartile range [IQR]) antibody titer against the receptor-binding domain (RBD) of the spike (S) protein after the third dose (10,358.0 U/mL [IQR = 673.9-31,753.0]) was significantly higher than that after the first (10.2 U/mL [IQR = 0.6-37.0]) and the second doses (125.6 U/mL [IQR = 2.8-1251.0]) (P < .0001). The haploidentical donor status was an independent risk factor (adjusted odds ratio = 7.67, 95% confidence interval [CI], 1.86-31.60) for suboptimal antibody response (anti-RBD < 100 U/mL). S-specific CD4+ and CD8+ T-cell responses were measured in a subset of Allo-SCT recipients (n = 20) by flow cytometry. Most developed antigen-specific CD4+ (55%-80%) and CD8+ T-cells (80%) after 2 doses of vaccine. Frequencies of CD4+ polyfunctional (P = .020) and IL-2 monofunctional (P = .013) T-cells significantly increased after the third dose. Twenty-three episodes (23/301 doses [7.6%]) of new-onset or worsening pre-existing graft-versus-host disease (GVHD) occurred, including 4 episodes after the third dose. We observed 4 relapses (3.27%). Seven patients developed SARS-CoV-2 infection despite vaccination, although none required hospitalization. In conclusion, the 3-dose SARS-CoV-2 vaccine schedule provided immunity associated with a low risk of GVHD and other adverse effects. This prospective cohort showed that the third dose of SARS-CoV-2 vaccine in allogeneic stem cell transplant recipients promoted better humoral and cellar immune responses than after the initial series without increasing the risk of GVHD or severe adverse effects.