medwireNews: Among people treated with anti-CD20 B cell-depleting agents, timing of treatment and numbers of circulating CD4+ and CD19+ cells are significant predictors of immune responses to messenger (m)RNA vaccines against SARS-CoV-2, shows the RituxiVac study.
“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,” write the researchers in The Lancet Rheumatology.
The study population included 96 people with a history of rituximab or ocrelizumab therapy for autoimmune disease (74%), transplantation (20%), or cancer (6%), with a median time since the last anti-CD20 treatment of 1.07 years. The most common indication for these therapies was antineutrophil cytoplasmic antibody-associated vasculitis (21%), followed by transplantation (20%), while rheumatoid arthritis, Sjögren’s syndrome, systemic lupus erythematosus, and B cell lymphoma each affected 6% of patients.
In accordance with previous studies, immune responses at least 4 weeks after complete vaccination with the Pfizer–BioNTech (BNT162b2) or Moderna (mRNA-1273) vaccine were blunted in these people relative to 29 immunocompetent controls.
Specifically, patients treated with B cell-depleting therapy were significantly less likely than controls to have humoral immune responses according to the presence of immunoglobulin G antibodies against the SARS-CoV-2 spike protein (49 vs 100%), cell-mediated responses according to SARS-CoV-2-specific interferon γ release (20 vs 75%), or both (14 vs 75%).
The RituxiVac investigators then carried out multivariable analyses, finding that anti-CD20 therapy timing and peripheral CD4+ and CD19+ cell counts were significant independent predictors of humoral response to vaccination among patients on B cell-depleting therapy, while concomitant immunosuppression predicted a blunted response.
Area under the receiver operating characteristic curve analysis demonstrated that time of more than 7.6 months since last anti-CD20 therapy (positive predictive value [PPV]=0.78), peripheral CD19+ cell count of more than 27 cells/μL (PPV=0.70), and CD4+ lymphocyte count of more than 653 cells/μL (PPV=0.71) predicted humoral immune response, with accuracies of 66–67%.
“If the predictive potential of CD4+ T-helper-cell counts as an immune biomarker for SARS-CoV-2 mRNA-based vaccines is confirmed in future prospective studies, individually tailored but easily applicable vaccination strategies could be derived,” say Daniel Sidler and colleagues from the University of Bern in Switzerland.
They add: “[W]e propose that a simple peripheral count of CD4+ cells could serve as a starting point to stratify patients according to anticipated vaccination response, even in patients with recent or severe B-cell depletion, or both.”
Sidler and team also note that patients who received the mRNA-1273 vaccine (n=38) had “more pronounced responses” those given the Pfizer–BioNTech vaccine (n=58), but they say “this finding should be interpreted with caution” in light of “the comparatively lower number of individuals who received the mRNA-1273 vaccine.”
medwireNews is an independent medical news service provided by Springer Healthcare Ltd. © 2021 Springer Healthcare Ltd, part of the Springer Nature Group
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