Reduced Efficacy of SARS-CoV-2 mRNA Vaccines in Patients With CD20 B-Cell-Depleting Treatment History

Antibodies attacking coronavirus particle
Antibodies attacking a coronavirus particle, illustration.
Researchers assessed the humoral and cell-mediated immune responses to SARS-CoV-2 mRNA-based vaccines in patients with a history of receiving CD20-targeted B-cell-depleting therapy.

The humoral and cell-mediated immune responses elicited by SARS-CoV-2 messenger RNA (mRNA) vaccines are blunted in patients with a history of CD20 B-cell-depleting therapy, according to study results published in Lancet Rheumatology.

Previous studies have shown that age, the male sex, preexisting autoimmune disease, kidney disease, and malignancy are associated with an increased risk for severe COVID-19. Although mRNA vaccines had high efficacy in randomized clinical trials, limited data are available on the efficacy of SARS-CoV-2 mRNA vaccines in patients receiving CD-20 B-cell-depleting agents.

The RituxiVac trial ( Identifier: NCT04877496) is an open-label study including patients from the Bern University Hospital in Switzerland with a history of treatment with rituximab or ocrelizumab and no prior history of SARS-CoV-2 infection.

A team of researchers investigated humoral and cell-mediated immune responses to SARS-CoV-2 mRNA-based vaccines in patients who received CD20 B-cell-depleting agents for the treatment of autoimmune diseases, transplantation, or malignancy.

The immune responses were determined by serum antibody measurement, analysis of lymphocyte subpopulation and interferon-γ release assay at least 4 weeks after completing the vaccination series. The study also included a control group of healthy adults without a history of SARS-CoV-2 infection who received both the vaccine doses.

Primary outcome of the study was the percentage of patients with a history of anti-CD20 treatment who had a humoral immune response against the SARS-CoV-2 spike protein compared with healthy control participants. Secondary endpoints included the effect of time since the last anti-CD20 therapy and cumulative dose on immune responses to mRNA vaccine, and biomarkers of immunocompetence.

The study sample included 96 patients with a history of anti-CD20 therapy (median age, 67 years; 53% women) and 29 immunocompetent control participants (median age, 54 years; 66% women).

Humoral responses after SARS-CoV-2 mRNA vaccines, as determined by antispike immunoglobulin (Ig) G antibodies, were observed in all healthy control participants, but in only 49% of those with a history of receiving anti-CD20 therapy. Cell-mediated immune responses to vaccination, as determined by SARS-CoV-2 interferon (IFN)-γ release, was determined in 94 patients and observed in 20%of patients and 75% of t healthy control participants (P <.001).

Overall, 75% of the control participants compared with 14% of patients with a history of anti-CD20 therapy tested double-positive for humoral and cell-mediated response. Approximately half of patients who received treatment with anti-CD20 tested double-negative for antispike IgG and cell-mediated responses compared with the healthy controls.

Multivariable linear regression analysis for humoral and cellular anti-SARS-CoV-2 responses showed that cumulative dose of anti-CD20 therapy, CD19+ cells per μL, and time from last treatment were independent predictors of anti-SARS-CoV-2 spike IgG and IFN-γ release with optimal cutoffs at more than 7.6 months from the last treatment (positive predictive value, 0.78), and more than 27 CD19+ cells per μL (positive predictive value, 0.70).

The study had several limitations, including the heterogeneous study population, lack of data on serum antibodies against SARS-CoV-2 before vaccination, and differences in distribution of vaccines manufactured by Pfizer-BioNTech and Moderna between the control participants and patients.

“Following validation in independent cohorts in a prospective setting, these results could provide guidance for coordinating both the administration of SARS-CoV-2 vaccines and B-cell-depleting agents in this population,” the researchers concluded.


Moor MB, Suter-Riniker F, Horn MP, et al. Humoral and cellular responses to mRNA vaccines against SARS-CoV-2 in patients with a history of CD20 B-cell-depleting therapy (RituxiVac): an investigator-initiated, single-centre, open-label study. Lancet Rheumatol. Published online September 7, 2021. doi:10.1016/S2665-9913(21)00251-4