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

• Published in: British journal of haematology Vol. 202; no. 6; pp. 1091 - 1103
• Main Authors: Pinder, Christopher L, Jankovic, Dylan, Fox, Thomas A, Kirkwood, Amy, Enfield, Louise, Alrubayyi, Aljawharah, Touizer, Emma, Ford, Rosemarie, Pocock, Rachael, Shin, Jin-Sup, Ziegler, Joseph, Thomson, Kirsty J, Ardeshna, Kirit M, Peppa, Dimitra, McCoy, Laura E, Morris, Emma C
• Format: Journal Article
• Language: English
• Published: England Blackwell Publishing Ltd 01.09.2023; John Wiley and Sons Inc
• Subjects: Antibodies, Viral; Cell size; COVID-19; COVID-19 - prevention & control; COVID-19 Vaccines; Enzyme-linked immunosorbent assay; Flow cytometry; Hematologic Neoplasms - therapy; Hematology; Humans; Immunization; Immunoglobulin G; Malignancy; Original Paper; SARS-CoV-2; Seroconversion; Severe acute respiratory syndrome coronavirus 2; Vaccination; haematological malignancies; infection; antibodies; B cells; T cells; vaccines
• ISSN: 0007-1048; 1365-2141
• DOI: 10.1111/bjh.18962

Patients 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.