Rituximab‐treated patients with lymphoma develop strong CD8 T‐cell responses following COVID‐19 vaccination

Abstract

Summary B‐cell depletion induced by anti‐cluster of differentiation 20 (CD20) monoclonal antibody (mAb) therapy of patients with lymphoma is expected to impair humoral responses to severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2) vaccination, but effects on CD8 T‐cell responses are unknown. Here, we investigated humoral and CD8 T‐cell responses following two vaccinations in patients with lymphoma undergoing anti‐CD20‐mAb therapy as single agent or in combination with chemotherapy or other anti‐neoplastic agents during the last 9 months prior to inclusion, and in healthy age‐matched blood donors. Antibody measurements showed that seven of 110 patients had antibodies to the receptor‐binding domain of the SARS‐CoV‐2 Spike protein 3–6 weeks after the second dose of vaccination. Peripheral blood CD8 T‐cell responses against prevalent human leucocyte antigen (HLA) class I SARS‐CoV‐2 epitopes were determined by peptide‐HLA multimer analysis. Strong CD8 T‐cell responses were observed in samples from 20/29 patients (69%) and 12/16 (75%) controls, with similar median response magnitudes in the groups and some of the strongest responses observed in patients. We conclude that despite the absence of humoral immune responses in fully SARS‐CoV‐2‐vaccinated, anti‐CD20‐treated patients with lymphoma, their CD8 T‐cell responses reach similar frequencies and magnitudes as for controls. Patients with lymphoma on B‐cell depleting therapies are thus likely to benefit from current coronavirus disease 2019 (COVID‐19) vaccines, and development of vaccines aimed at eliciting T‐cell responses to non‐Spike epitopes might provide improved protection.

Comprehensive analysis of immune responses in CLL patients after heterologous COVID-19 vaccination

“…10,23,48 T cells are especially critical in immune protection against SARS-CoV-2 in cancer patients, who undergo therapy with B cell depleting agents, such as anti-CD20 antibody. 49,50 Here we report that CLL patients with for use under a CC0 license. This article is a US Government work.…”

Can B cell‐deficient patients rely on COVID‐19 vaccine‐induced T‐cell immunity?

“…20 Interestingly, several of these include only T cell epitopes without the ability to induce neutralising antibodies, and thus would likely function best as boosters, even in B cell-deficient patients, some of whom may still generate antibody responses. The observation that T cell epitopes may suffer less from mutational escape by variants [21][22][23] is a potential benefit of vaccines targeting T cells, and Riise et al 15 demonstrate this to be true for the epitopes they studied. In designing vaccines with T cell epitopes, it will be crucial to incorporate peptides covering HLA types prevalent in as much of the global population as possible, either in one pool or in specific pools for specific populations.…”

“…or upregulation of cell surface activation markers. Riise et al 15 applied a different approach. They evaluated vaccineinduced CD8 T cell responses to defined immunogenic spike epitopes identified in convalescent patients 16 and quantified responding cells using fluorescently tagged peptide-bound HLA multimers.…”

“…In their paper Riise et al 15 further our understanding of T cell responses in B cell‐deficient patients. They studied patients with B cell lymphoma who had received two doses of COVID‐19 vaccination and all of whom had received rituximab within the past 8 months.…”

“…T cell vaccine responses are commonly evaluated by ex vivo stimulation of peripheral T cells with spike protein peptide pools to identify SARS‐CoV‐2‐specific T cells by cytokine production or upregulation of cell surface activation markers. Riise et al 15 applied a different approach. They evaluated vaccine‐induced CD8 T cell responses to defined immunogenic spike epitopes identified in convalescent patients 16 and quantified responding cells using fluorescently tagged peptide‐bound HLA multimers.…”