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

Simple Summary Anti-CD20 treatments produce a prolonged B-cell aplasia that is responsible for a suboptimal humoral response after vaccination against SARS-CoV-2, even months after receiving therapy. However, there is scarce information on the cellular immune response. In this study, we analyzed both cellular and humoral immune responses against SARS-CoV-2 in 18 patients treated with rituximab after receiving a COVID-19 vaccine booster dose. These studies are essential to design an efficient vaccination schedule for these individuals. Although we did not observe a significant benefit in the cellular immune response, there was an increase in the humoral response after the booster dose in rituximab-treated patients in comparison with the response after the second dose, likely due to a longer period of time since the last treatment with rituximab (9.6 versus 13.8 months, respectively). This excellent humoral response was observed even with reduced levels of total B cells, and it was likely responsible for the prevention of severe disease in individuals who acquired a breakthrough infection. 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.