Humoral and cellular responses to SARS‐CoV‐2 in patients with B‐cell haematological malignancies improve with successive vaccination

Abstract

SummaryPatients with haematological malignancies are more likely to have poor responses to vaccination. Here we provide detailed analysis of the humoral and cellular responses to COVID‐19 vaccination in 69 patients with B‐cell malignancies. Measurement of anti‐spike IgG in serum demonstrated a low seroconversion rate with 27.1% and 46.8% of patients seroconverting after the first and second doses of vaccine, respectively. In vitro pseudoneutralisation assays demonstrated a poor neutralising response, with 12.5% and 29.5% of patients producing a measurable neutralising titre after the first and second doses, respectively. A third dose increased seropositivity to 54.3% and neutralisation to 51.5%, while a fourth dose further increased both seropositivity and neutralisation to 87.9%. Neutralisation titres post‐fourth dose showed a positive correlation with the size of the B‐cell population measured by flow cytometry, suggesting an improved response correlating with recovery of the B‐cell compartment after B‐cell depletion treatments. In contrast, interferon gamma ELISpot analysis showed a largely intact T‐cell response, with the percentage of patients producing a measurable response boosted by the second dose to 75.5%. This response was maintained thereafter, with only a small increase following the third and fourth doses, irrespective of the serological response at these timepoints.

Sequential cellular and humoral responses after repetitive COVID‐19 vaccination in patients treated with anti‐CD20 antibodies

“…A previous study that investigated cellular responses after the fourth vaccination among patients with lymphoid neoplasms reported enhanced cellular responses before and after the fourth vaccination. 13,14 Our results align with those of previous studies, demonstrating that the third and fourth vaccinations increased cellular responders to 55% after the third dose and 59% after the fourth dose, from 41% before the third dose. This response was unrelated to the B-cell status, suggesting that additional vaccinations may offer potential benefits in enhancing cellular immunity, even in cases where seroconversion is not achieved.…”

“…Cellular responses against SARS‐CoV‐2 in seronegative patients after mRNA COVID‐19 vaccination have been reported, 5,12 indicating the potential benefits of vaccination even in the absence of a humoral response. A previous study that investigated cellular responses after the fourth vaccination among patients with lymphoid neoplasms reported enhanced cellular responses before and after the fourth vaccination 13,14 . Our results align with those of previous studies, demonstrating that the third and fourth vaccinations increased cellular responders to 55% after the third dose and 59% after the fourth dose, from 41% before the third dose.…”