Humoral and cellular immunogenicity of SARS-CoV-2 vaccines in chronic lymphocytic leukemia: a prospective cohort study.

ABSTRACT: Chronic lymphocytic leukemia (CLL), the most common leukemia worldwide, is associated with increased COVID-19 mortality. Previous studies suggest only a proportion of vaccinated CLL patients develop SARS-CoV-2 spike antibodies. Whether the elicited antibodies are functional and/or accompanied by functional T-cell responses is unknown. This prospective cohort study (NCT05007860) included patients with CLL who received SARS-CoV-2 and PCV13 vaccines (not concurrently). The primary cohort included adults with CLL off therapy. Co-primary outcomes were serologic response to SARS-CoV-2 (receptor binding domain [RBD]-immunoassay) and PCV13 vaccines (23-serotype IgG assay). Characterization of SARS-CoV-2 antibodies and their functional activity and assessment of functional T-cell responses were performed. Sixty percent (18/30) of patients demonstrated serologic responses to SARS-CoV-2 vaccination, appearing more frequent among treatment-naïve patients (72%). Among treatment-naïve patients, an absolute lymphocyte count ≤24,000/uL was associated with serologic response (94% vs 14%, p<0.001). On interferon gamma release assays, 80% (16/20) of patients had functional spike-specific T-cell responses, including 78% (7/9) with a negative RBD-immunoassay, a group enriched for prior B-cell depleting therapies. A bead-based multiplex immunoassay identified antibodies against wildtype and variant SARS-CoV-2 (alpha, beta, gamma, and delta) in all tested patients, and confirmed Fc-receptor binding and effector functions of these antibodies. Of 11 patients with negative RBD-immunoassay post-vaccination, 6 (55%) responded to an additional mRNA-based vaccine dose. The PCV13 serologic response rate was 29% (8/28). Our data demonstrate that SARS-CoV-2 vaccination induces functional T-cell and antibody responses in CLL patients and provides the framework for investigating the molecular mechanisms and clinical benefit of these responses. This trial is registered at www.clinicaltrials.gov as NCT05007860.

SUBMITTER: Haydu JE 

PROVIDER: S-EPMC8789382 | biostudies-literature |

REPOSITORIES: biostudies-literature