Strong Humoral but Not Cellular Immune Responses against SARS-CoV-2 in Individuals with Oncohematological Disease Who Were Treated with Rituximab before Receiving a Vaccine Booster

Abstract

The humoral immune response developed after receiving the full vaccination schedule against COVID-19 is impaired in individuals who received anti-CD20 therapy 6–9 months before vaccination. However, there is little information about the cellular immune responses elicited in these individuals. In this study, we analyzed the humoral and cellular immune responses in 18 individuals with hematological disease who received the last dose of rituximab 13.8 months (IQR 9.4–19) before the booster dose. One month after receiving the booster dose, the seroconversion rate in the rituximab-treated cohort increased from 83.3% to 88.9% and titers of specific IgGs against SARS-CoV-2 increased 1.53-fold (p = 0.0098), while the levels of neutralizing antibodies increased 3.03-fold (p = 0.0381). However, the cytotoxic activity of peripheral blood mononuclear cells (PBMCs) from rituximab-treated individuals remained unchanged, and both antibody-dependent cellular cytotoxicity (ADCC) and direct cellular cytotoxicity (CDD) were reduced 1.7-fold (p = 0.0047) and 2.0-fold (p = 0.0086), respectively, in comparison with healthy donors. Breakthrough infections rate was higher in our cohort of rituximab-treated individuals (33.33%), although most of the infected patients (83.4%) developed a mild form of COVID-19. In conclusion, our findings confirm a benefit in the humoral, but not in the cellular, immune response in rituximab-treated individuals after receiving a booster dose of an mRNA-based vaccine against COVID-19.

The immunologic outcomes and adverse events of COVID-19 vaccine booster dose in immunosuppressed people: A systematic review

“…Four studies were conducted among MS and/or patients undergoing Anti-CD20 treatment ( Torres et al, 2022 , Madelon et al, 2022 , Maniscalco et al, 2022 , Moser et al, 2022 ). Madelon et al, in their study of 20 MS patients treated with anti-CD20 drugs, reported that the levels of cytotoxic T cells, specific for the vaccine strain, Delta, and Omicron variants, increased after the 3rd dose ( Madelon et al, 2022 ).…”

“…One study of 15 MS patients on anti-CD20 treatments found that the antibody levels were significantly higher among patients who only received the booster dose amid B cell depletion comparing to patients vaccinated during a continuous state of B cell depletion ( Moser et al, 2022 ). Torres et al reported an increase of 1.53-fold in SARS-CoV-2 Specific IgGs in rituximab-treated patients compared to a 2.47-fold increase in healthy donors one month after receiving the booster dose, they also noted that 100 % of healthy controls and 88.9 % of rituximab-treated patients showed SARS-CoV-2 IgGs after the booster dose ( Torres et al, 2022 ).…”

“…Therefore, impaired immune response necessitates repeated booster doses particularly in vulnerable and immunocompromised patients ( Affeldt et al, 2022 , Yang et al, 2022 , Lin et al, 2022 ). Furthermore, some studies have demonstrated that decreasing T-cell (cellular) immunity is not parallel to waning antibody (humoral) response after the booster dose ( Lin et al, 2022 , Torres et al, 2022 ) and reduction in disease severity is not completely based on measured humoral response ( Hod et al, 2023 ); but the exact roles are not completely known ( Wroński et al, 2022 ). Although these groups of patients were excluded from clinical trials for marketing authorization, based on findings of different studies administration of a third ( Goldwater et al, 2023 , Feingold et al, 2022 ) and in some cases a fourth dose ( Davidov et al, 2022 , Fendler et al, 2022 ) of vaccine is recommended in immunocompromised patients.…”